The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform
Zafar K. Khan - One of the best experts on this subject based on the ideXlab platform.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax (11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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Impact of dendritic cells and adjuvant on the in vivo immunogenicity of HTLV-1 Tax 11-19 epitope in Hybrid HLA-A2.1/DTR transgenic mice
Retrovirology, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Saifur Rahman, Pooja Jain, Zafar K. KhanAbstract:Individually, HLA-A2.1 and CD11c-DTR transgenic Mouse Strains have been used to investigate the immunopathogenesis of different viruses and have provided important insights into current understanding of hostpathogen interactions during human T-cell leukemia virus type 1 (HTLV-1) infection. Here, these mice enabled the study of the CD8 T-cell immune response against a known MHC class I HLA-A2.1-restricted epitope 11-19 of the viral oncoprotein Tax delivered along with tetanus helper peptide without or with incomplete Freund’s adjuvant (IFA) in the absence and presence of dendritic cells (DCs). First, a cross breeding strategy was utilized to generate a HLA-A2.1/DTR Hybrid Strain that carries an HLA-A2.1 gene and diphtheria toxin receptor gene for in vivo depletion of CD11c DCs. Upon in vitro stimulation of splenocytes from immunized mice with autologous bone marrow-derived DCs primed with Tax11-19 antigen, DC-depleted mice showed marked attenuation in the proliferation of CD8 T-cells when compared with the non DC-depleted mice. Additionally, mice immunized with adjuvant demonstrated a much higher frequency of Tax11-19-specific cells response but overall reduced proliferation compared to the non-adjuvant group. A significantly high serum level of IL-6 coincided with depletion of DCs while a decrease in TGF-b cytokine associated with adjuvant use irrespective of DCs’ presence. In conclusion, these studies not only demonstrate that the clinically characterized Tax epitope 11-19 can be a potential candidate for the DC-based anti-HTLV-1 vaccine but also illustrate a broader application of the new HLA-A2.1/DTR-transgenic Hybrid Mouse Strain as an important tool to investigate DC involvement in human class-I-restricted immune responses.
Divya Sagar - One of the best experts on this subject based on the ideXlab platform.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax (11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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Impact of dendritic cells and adjuvant on the in vivo immunogenicity of HTLV-1 Tax 11-19 epitope in Hybrid HLA-A2.1/DTR transgenic mice
Retrovirology, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Saifur Rahman, Pooja Jain, Zafar K. KhanAbstract:Individually, HLA-A2.1 and CD11c-DTR transgenic Mouse Strains have been used to investigate the immunopathogenesis of different viruses and have provided important insights into current understanding of hostpathogen interactions during human T-cell leukemia virus type 1 (HTLV-1) infection. Here, these mice enabled the study of the CD8 T-cell immune response against a known MHC class I HLA-A2.1-restricted epitope 11-19 of the viral oncoprotein Tax delivered along with tetanus helper peptide without or with incomplete Freund’s adjuvant (IFA) in the absence and presence of dendritic cells (DCs). First, a cross breeding strategy was utilized to generate a HLA-A2.1/DTR Hybrid Strain that carries an HLA-A2.1 gene and diphtheria toxin receptor gene for in vivo depletion of CD11c DCs. Upon in vitro stimulation of splenocytes from immunized mice with autologous bone marrow-derived DCs primed with Tax11-19 antigen, DC-depleted mice showed marked attenuation in the proliferation of CD8 T-cells when compared with the non DC-depleted mice. Additionally, mice immunized with adjuvant demonstrated a much higher frequency of Tax11-19-specific cells response but overall reduced proliferation compared to the non-adjuvant group. A significantly high serum level of IL-6 coincided with depletion of DCs while a decrease in TGF-b cytokine associated with adjuvant use irrespective of DCs’ presence. In conclusion, these studies not only demonstrate that the clinically characterized Tax epitope 11-19 can be a potential candidate for the DC-based anti-HTLV-1 vaccine but also illustrate a broader application of the new HLA-A2.1/DTR-transgenic Hybrid Mouse Strain as an important tool to investigate DC involvement in human class-I-restricted immune responses.
Todd D. Schell - One of the best experts on this subject based on the ideXlab platform.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax (11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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Impact of dendritic cells and adjuvant on the in vivo immunogenicity of HTLV-1 Tax 11-19 epitope in Hybrid HLA-A2.1/DTR transgenic mice
Retrovirology, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Saifur Rahman, Pooja Jain, Zafar K. KhanAbstract:Individually, HLA-A2.1 and CD11c-DTR transgenic Mouse Strains have been used to investigate the immunopathogenesis of different viruses and have provided important insights into current understanding of hostpathogen interactions during human T-cell leukemia virus type 1 (HTLV-1) infection. Here, these mice enabled the study of the CD8 T-cell immune response against a known MHC class I HLA-A2.1-restricted epitope 11-19 of the viral oncoprotein Tax delivered along with tetanus helper peptide without or with incomplete Freund’s adjuvant (IFA) in the absence and presence of dendritic cells (DCs). First, a cross breeding strategy was utilized to generate a HLA-A2.1/DTR Hybrid Strain that carries an HLA-A2.1 gene and diphtheria toxin receptor gene for in vivo depletion of CD11c DCs. Upon in vitro stimulation of splenocytes from immunized mice with autologous bone marrow-derived DCs primed with Tax11-19 antigen, DC-depleted mice showed marked attenuation in the proliferation of CD8 T-cells when compared with the non DC-depleted mice. Additionally, mice immunized with adjuvant demonstrated a much higher frequency of Tax11-19-specific cells response but overall reduced proliferation compared to the non-adjuvant group. A significantly high serum level of IL-6 coincided with depletion of DCs while a decrease in TGF-b cytokine associated with adjuvant use irrespective of DCs’ presence. In conclusion, these studies not only demonstrate that the clinically characterized Tax epitope 11-19 can be a potential candidate for the DC-based anti-HTLV-1 vaccine but also illustrate a broader application of the new HLA-A2.1/DTR-transgenic Hybrid Mouse Strain as an important tool to investigate DC involvement in human class-I-restricted immune responses.
Shet Masih - One of the best experts on this subject based on the ideXlab platform.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax (11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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Impact of dendritic cells and adjuvant on the in vivo immunogenicity of HTLV-1 Tax 11-19 epitope in Hybrid HLA-A2.1/DTR transgenic mice
Retrovirology, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Saifur Rahman, Pooja Jain, Zafar K. KhanAbstract:Individually, HLA-A2.1 and CD11c-DTR transgenic Mouse Strains have been used to investigate the immunopathogenesis of different viruses and have provided important insights into current understanding of hostpathogen interactions during human T-cell leukemia virus type 1 (HTLV-1) infection. Here, these mice enabled the study of the CD8 T-cell immune response against a known MHC class I HLA-A2.1-restricted epitope 11-19 of the viral oncoprotein Tax delivered along with tetanus helper peptide without or with incomplete Freund’s adjuvant (IFA) in the absence and presence of dendritic cells (DCs). First, a cross breeding strategy was utilized to generate a HLA-A2.1/DTR Hybrid Strain that carries an HLA-A2.1 gene and diphtheria toxin receptor gene for in vivo depletion of CD11c DCs. Upon in vitro stimulation of splenocytes from immunized mice with autologous bone marrow-derived DCs primed with Tax11-19 antigen, DC-depleted mice showed marked attenuation in the proliferation of CD8 T-cells when compared with the non DC-depleted mice. Additionally, mice immunized with adjuvant demonstrated a much higher frequency of Tax11-19-specific cells response but overall reduced proliferation compared to the non-adjuvant group. A significantly high serum level of IL-6 coincided with depletion of DCs while a decrease in TGF-b cytokine associated with adjuvant use irrespective of DCs’ presence. In conclusion, these studies not only demonstrate that the clinically characterized Tax epitope 11-19 can be a potential candidate for the DC-based anti-HTLV-1 vaccine but also illustrate a broader application of the new HLA-A2.1/DTR-transgenic Hybrid Mouse Strain as an important tool to investigate DC involvement in human class-I-restricted immune responses.
Pooja Jain - One of the best experts on this subject based on the ideXlab platform.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax (11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Retrovirology, 2015Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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in vivo immunogenicity of tax 11 19 epitope in hla a2 dtr transgenic mice implication for dendritic cell based anti htlv 1 vaccine
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.
Vaccine, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Pooja Jain, Steven Jacobson, Joseph D Comber, Ramila Philip, Brian Wigdahl, Zafar K. KhanAbstract:Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR Hybrid Mouse Strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly Hybrid Mouse Strain could be used for investigating DC involvement in human class-I-restricted immune responses.
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Impact of dendritic cells and adjuvant on the in vivo immunogenicity of HTLV-1 Tax 11-19 epitope in Hybrid HLA-A2.1/DTR transgenic mice
Retrovirology, 2014Co-Authors: Divya Sagar, Shet Masih, Todd D. Schell, Saifur Rahman, Pooja Jain, Zafar K. KhanAbstract:Individually, HLA-A2.1 and CD11c-DTR transgenic Mouse Strains have been used to investigate the immunopathogenesis of different viruses and have provided important insights into current understanding of hostpathogen interactions during human T-cell leukemia virus type 1 (HTLV-1) infection. Here, these mice enabled the study of the CD8 T-cell immune response against a known MHC class I HLA-A2.1-restricted epitope 11-19 of the viral oncoprotein Tax delivered along with tetanus helper peptide without or with incomplete Freund’s adjuvant (IFA) in the absence and presence of dendritic cells (DCs). First, a cross breeding strategy was utilized to generate a HLA-A2.1/DTR Hybrid Strain that carries an HLA-A2.1 gene and diphtheria toxin receptor gene for in vivo depletion of CD11c DCs. Upon in vitro stimulation of splenocytes from immunized mice with autologous bone marrow-derived DCs primed with Tax11-19 antigen, DC-depleted mice showed marked attenuation in the proliferation of CD8 T-cells when compared with the non DC-depleted mice. Additionally, mice immunized with adjuvant demonstrated a much higher frequency of Tax11-19-specific cells response but overall reduced proliferation compared to the non-adjuvant group. A significantly high serum level of IL-6 coincided with depletion of DCs while a decrease in TGF-b cytokine associated with adjuvant use irrespective of DCs’ presence. In conclusion, these studies not only demonstrate that the clinically characterized Tax epitope 11-19 can be a potential candidate for the DC-based anti-HTLV-1 vaccine but also illustrate a broader application of the new HLA-A2.1/DTR-transgenic Hybrid Mouse Strain as an important tool to investigate DC involvement in human class-I-restricted immune responses.
