The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Francesca Fallarino - One of the best experts on this subject based on the ideXlab platform.
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the combined effects of tryptophan starvation and tryptophan catabolites down regulate t cell receptor ζ chain and induce a regulatory phenotype in naive t cells
Journal of Immunology, 2006Co-Authors: Francesca Fallarino, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Ursula Grohmann, Maria Laura Belladonna, Barbara C Mcgrath, Douglas R Cavener, Claudia Volpi, Pere SantamariaAbstract:Tryptophan Catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan Catabolism affects T cell responses remain unclear. We provide evidence that the short-term, combined effects of tryptophan deprivation and tryptophan catabolites result in GCN2 kinase-dependent down-regulation of the TCR ζ-chain in murine CD8+ T cells. TCR ζ down-regulation can be demonstrated in vivo and is associated with an impaired cytotoxic effector function in vitro. The longer-term effects of tryptophan Catabolism include the emergence of a regulatory phenotype in naive CD4+CD25− T cells via TGF-β induction of the forkhead transcription factor Foxp3. Such converted cells appear to be CD25+, CD69−, CD45RBlow, CD62L+, CTLA-4+, BTLAlow and GITR+, and are capable of effective control of diabetogenic T cells when transferred in vivo. Thus, both tryptophan starvation and tryptophan catabolites contribute to establishing a regulatory environment affecting CD8+ as well as CD4+ T cell function, and not only is tryptophan Catabolism an effector mechanism of tolerance, but it also results in GCN2-dependent generation of autoimmune-preventive regulatory T cells.
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Modulation of tryptophan Catabolism by regulatory T cells
Nature Immunology, 2003Co-Authors: Francesca Fallarino, Ciriana Orabona, Kwang Woo Hwang, Carmine Vacca, Roberta Bianchi, Ursula Grohmann, Maria Laura Belladonna, Maria Cristina Fioretti, Maria-luisa Alegre, Paolo PuccettiAbstract:Regulatory T (T_R) cells manifest constitutive expression of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), but the function of CTLA-4 in mediating the regulatory function of T_R cells is unclear. We show here that mouse CD4^+CD25^+ cells, either resting or induced to overexpress CTLA-4 by treatment with antibody to CD3, initiated tryptophan Catabolism in dendritic cells through a CTLA-4-dependent mechanism. This process required B7 expression and cytokine production by the dendritic cells. In contrast, T_R cells cultured in the presence of bacterial lipopolysaccharide induced tryptophan Catabolism by dendritic cells in a CTLA-4-independent but cytokine-dependent way. Thus, regulation of immunosuppressive tryptophan Catabolism in dendritic cells might represent a major mechanism of action of T_R cells.
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a defect in tryptophan Catabolism impairs tolerance in nonobese diabetic mice
Journal of Experimental Medicine, 2003Co-Authors: Ursula Grohmann, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Maria Cristina Fioretti, Francesca Fallarino, Paolo PuccettiAbstract:The predisposition of nonobese diabetic (NOD) mice to develop autoimmunity reflects deficiencies in both peripheral and central tolerance. Several defects have been described in these mice, among which aberrant antigen-presenting cell function and peroxynitrite formation. Prediabetes and diabetes in NOD mice have been targeted with different outcomes by a variety of immunotherapies, including interferon (IFN)-γ. This cytokine may be instrumental in specific forms of tolerance by virtue of its ability to activate immunosuppressive tryptophan Catabolism. Here, we provide evidence that IFN-γ fails to induce tolerizing properties in dendritic cells from highly susceptible female mice early in prediabetes. This effect is associated with impaired tryptophan Catabolism, is related to transient blockade of the Stat1 pathway of intracellular signaling by IFN-γ, and is caused by peroxynitrite production. However, the use of a peroxynitrite inhibitor can rescue tryptophan Catabolism and tolerance in those mice. This is the first report of an experimental autoimmune disease in which defective tolerance is causally linked to impaired tryptophan Catabolism.
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ctla 4 ig regulates tryptophan Catabolism in vivo
Nature Immunology, 2002Co-Authors: Ursula Grohmann, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Maria Laura Belladonna, Francesca Fallarino, Filippo Calcinaro, Alberto Falorni, Paola Candeloro, Maria Cristina FiorettiAbstract:Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a critical role in peripheral tolerance. However, regulatory pathways initiated by the interactions of CTLA-4 with B7 counterligands expressed on antigen-presenting cells are not completely understood. We show here that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4-immunoglobulin (CTLA-4-Ig) is contingent upon effective tryptophan Catabolism in the host. In vitro, we show that CTLA-4-Ig regulates cytokine-dependent tryptophan Catabolism in B7-expressing dendritic cells. These data suggest that modulation of tryptophan Catabolism is a means by which CTLA-4 functions in vivo and that CTLA-4 acts as a ligand for B7 receptor molecules that transduce intracellular signals.
Ursula Grohmann - One of the best experts on this subject based on the ideXlab platform.
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the combined effects of tryptophan starvation and tryptophan catabolites down regulate t cell receptor ζ chain and induce a regulatory phenotype in naive t cells
Journal of Immunology, 2006Co-Authors: Francesca Fallarino, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Ursula Grohmann, Maria Laura Belladonna, Barbara C Mcgrath, Douglas R Cavener, Claudia Volpi, Pere SantamariaAbstract:Tryptophan Catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan Catabolism affects T cell responses remain unclear. We provide evidence that the short-term, combined effects of tryptophan deprivation and tryptophan catabolites result in GCN2 kinase-dependent down-regulation of the TCR ζ-chain in murine CD8+ T cells. TCR ζ down-regulation can be demonstrated in vivo and is associated with an impaired cytotoxic effector function in vitro. The longer-term effects of tryptophan Catabolism include the emergence of a regulatory phenotype in naive CD4+CD25− T cells via TGF-β induction of the forkhead transcription factor Foxp3. Such converted cells appear to be CD25+, CD69−, CD45RBlow, CD62L+, CTLA-4+, BTLAlow and GITR+, and are capable of effective control of diabetogenic T cells when transferred in vivo. Thus, both tryptophan starvation and tryptophan catabolites contribute to establishing a regulatory environment affecting CD8+ as well as CD4+ T cell function, and not only is tryptophan Catabolism an effector mechanism of tolerance, but it also results in GCN2-dependent generation of autoimmune-preventive regulatory T cells.
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Modulation of tryptophan Catabolism by regulatory T cells
Nature Immunology, 2003Co-Authors: Francesca Fallarino, Ciriana Orabona, Kwang Woo Hwang, Carmine Vacca, Roberta Bianchi, Ursula Grohmann, Maria Laura Belladonna, Maria Cristina Fioretti, Maria-luisa Alegre, Paolo PuccettiAbstract:Regulatory T (T_R) cells manifest constitutive expression of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), but the function of CTLA-4 in mediating the regulatory function of T_R cells is unclear. We show here that mouse CD4^+CD25^+ cells, either resting or induced to overexpress CTLA-4 by treatment with antibody to CD3, initiated tryptophan Catabolism in dendritic cells through a CTLA-4-dependent mechanism. This process required B7 expression and cytokine production by the dendritic cells. In contrast, T_R cells cultured in the presence of bacterial lipopolysaccharide induced tryptophan Catabolism by dendritic cells in a CTLA-4-independent but cytokine-dependent way. Thus, regulation of immunosuppressive tryptophan Catabolism in dendritic cells might represent a major mechanism of action of T_R cells.
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a defect in tryptophan Catabolism impairs tolerance in nonobese diabetic mice
Journal of Experimental Medicine, 2003Co-Authors: Ursula Grohmann, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Maria Cristina Fioretti, Francesca Fallarino, Paolo PuccettiAbstract:The predisposition of nonobese diabetic (NOD) mice to develop autoimmunity reflects deficiencies in both peripheral and central tolerance. Several defects have been described in these mice, among which aberrant antigen-presenting cell function and peroxynitrite formation. Prediabetes and diabetes in NOD mice have been targeted with different outcomes by a variety of immunotherapies, including interferon (IFN)-γ. This cytokine may be instrumental in specific forms of tolerance by virtue of its ability to activate immunosuppressive tryptophan Catabolism. Here, we provide evidence that IFN-γ fails to induce tolerizing properties in dendritic cells from highly susceptible female mice early in prediabetes. This effect is associated with impaired tryptophan Catabolism, is related to transient blockade of the Stat1 pathway of intracellular signaling by IFN-γ, and is caused by peroxynitrite production. However, the use of a peroxynitrite inhibitor can rescue tryptophan Catabolism and tolerance in those mice. This is the first report of an experimental autoimmune disease in which defective tolerance is causally linked to impaired tryptophan Catabolism.
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ctla 4 ig regulates tryptophan Catabolism in vivo
Nature Immunology, 2002Co-Authors: Ursula Grohmann, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Maria Laura Belladonna, Francesca Fallarino, Filippo Calcinaro, Alberto Falorni, Paola Candeloro, Maria Cristina FiorettiAbstract:Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a critical role in peripheral tolerance. However, regulatory pathways initiated by the interactions of CTLA-4 with B7 counterligands expressed on antigen-presenting cells are not completely understood. We show here that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4-immunoglobulin (CTLA-4-Ig) is contingent upon effective tryptophan Catabolism in the host. In vitro, we show that CTLA-4-Ig regulates cytokine-dependent tryptophan Catabolism in B7-expressing dendritic cells. These data suggest that modulation of tryptophan Catabolism is a means by which CTLA-4 functions in vivo and that CTLA-4 acts as a ligand for B7 receptor molecules that transduce intracellular signals.
Paolo Puccetti - One of the best experts on this subject based on the ideXlab platform.
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Modulation of tryptophan Catabolism by regulatory T cells
Nature Immunology, 2003Co-Authors: Francesca Fallarino, Ciriana Orabona, Kwang Woo Hwang, Carmine Vacca, Roberta Bianchi, Ursula Grohmann, Maria Laura Belladonna, Maria Cristina Fioretti, Maria-luisa Alegre, Paolo PuccettiAbstract:Regulatory T (T_R) cells manifest constitutive expression of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), but the function of CTLA-4 in mediating the regulatory function of T_R cells is unclear. We show here that mouse CD4^+CD25^+ cells, either resting or induced to overexpress CTLA-4 by treatment with antibody to CD3, initiated tryptophan Catabolism in dendritic cells through a CTLA-4-dependent mechanism. This process required B7 expression and cytokine production by the dendritic cells. In contrast, T_R cells cultured in the presence of bacterial lipopolysaccharide induced tryptophan Catabolism by dendritic cells in a CTLA-4-independent but cytokine-dependent way. Thus, regulation of immunosuppressive tryptophan Catabolism in dendritic cells might represent a major mechanism of action of T_R cells.
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a defect in tryptophan Catabolism impairs tolerance in nonobese diabetic mice
Journal of Experimental Medicine, 2003Co-Authors: Ursula Grohmann, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Maria Cristina Fioretti, Francesca Fallarino, Paolo PuccettiAbstract:The predisposition of nonobese diabetic (NOD) mice to develop autoimmunity reflects deficiencies in both peripheral and central tolerance. Several defects have been described in these mice, among which aberrant antigen-presenting cell function and peroxynitrite formation. Prediabetes and diabetes in NOD mice have been targeted with different outcomes by a variety of immunotherapies, including interferon (IFN)-γ. This cytokine may be instrumental in specific forms of tolerance by virtue of its ability to activate immunosuppressive tryptophan Catabolism. Here, we provide evidence that IFN-γ fails to induce tolerizing properties in dendritic cells from highly susceptible female mice early in prediabetes. This effect is associated with impaired tryptophan Catabolism, is related to transient blockade of the Stat1 pathway of intracellular signaling by IFN-γ, and is caused by peroxynitrite production. However, the use of a peroxynitrite inhibitor can rescue tryptophan Catabolism and tolerance in those mice. This is the first report of an experimental autoimmune disease in which defective tolerance is causally linked to impaired tryptophan Catabolism.
Ciriana Orabona - One of the best experts on this subject based on the ideXlab platform.
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the combined effects of tryptophan starvation and tryptophan catabolites down regulate t cell receptor ζ chain and induce a regulatory phenotype in naive t cells
Journal of Immunology, 2006Co-Authors: Francesca Fallarino, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Ursula Grohmann, Maria Laura Belladonna, Barbara C Mcgrath, Douglas R Cavener, Claudia Volpi, Pere SantamariaAbstract:Tryptophan Catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan Catabolism affects T cell responses remain unclear. We provide evidence that the short-term, combined effects of tryptophan deprivation and tryptophan catabolites result in GCN2 kinase-dependent down-regulation of the TCR ζ-chain in murine CD8+ T cells. TCR ζ down-regulation can be demonstrated in vivo and is associated with an impaired cytotoxic effector function in vitro. The longer-term effects of tryptophan Catabolism include the emergence of a regulatory phenotype in naive CD4+CD25− T cells via TGF-β induction of the forkhead transcription factor Foxp3. Such converted cells appear to be CD25+, CD69−, CD45RBlow, CD62L+, CTLA-4+, BTLAlow and GITR+, and are capable of effective control of diabetogenic T cells when transferred in vivo. Thus, both tryptophan starvation and tryptophan catabolites contribute to establishing a regulatory environment affecting CD8+ as well as CD4+ T cell function, and not only is tryptophan Catabolism an effector mechanism of tolerance, but it also results in GCN2-dependent generation of autoimmune-preventive regulatory T cells.
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Modulation of tryptophan Catabolism by regulatory T cells
Nature Immunology, 2003Co-Authors: Francesca Fallarino, Ciriana Orabona, Kwang Woo Hwang, Carmine Vacca, Roberta Bianchi, Ursula Grohmann, Maria Laura Belladonna, Maria Cristina Fioretti, Maria-luisa Alegre, Paolo PuccettiAbstract:Regulatory T (T_R) cells manifest constitutive expression of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), but the function of CTLA-4 in mediating the regulatory function of T_R cells is unclear. We show here that mouse CD4^+CD25^+ cells, either resting or induced to overexpress CTLA-4 by treatment with antibody to CD3, initiated tryptophan Catabolism in dendritic cells through a CTLA-4-dependent mechanism. This process required B7 expression and cytokine production by the dendritic cells. In contrast, T_R cells cultured in the presence of bacterial lipopolysaccharide induced tryptophan Catabolism by dendritic cells in a CTLA-4-independent but cytokine-dependent way. Thus, regulation of immunosuppressive tryptophan Catabolism in dendritic cells might represent a major mechanism of action of T_R cells.
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a defect in tryptophan Catabolism impairs tolerance in nonobese diabetic mice
Journal of Experimental Medicine, 2003Co-Authors: Ursula Grohmann, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Maria Cristina Fioretti, Francesca Fallarino, Paolo PuccettiAbstract:The predisposition of nonobese diabetic (NOD) mice to develop autoimmunity reflects deficiencies in both peripheral and central tolerance. Several defects have been described in these mice, among which aberrant antigen-presenting cell function and peroxynitrite formation. Prediabetes and diabetes in NOD mice have been targeted with different outcomes by a variety of immunotherapies, including interferon (IFN)-γ. This cytokine may be instrumental in specific forms of tolerance by virtue of its ability to activate immunosuppressive tryptophan Catabolism. Here, we provide evidence that IFN-γ fails to induce tolerizing properties in dendritic cells from highly susceptible female mice early in prediabetes. This effect is associated with impaired tryptophan Catabolism, is related to transient blockade of the Stat1 pathway of intracellular signaling by IFN-γ, and is caused by peroxynitrite production. However, the use of a peroxynitrite inhibitor can rescue tryptophan Catabolism and tolerance in those mice. This is the first report of an experimental autoimmune disease in which defective tolerance is causally linked to impaired tryptophan Catabolism.
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ctla 4 ig regulates tryptophan Catabolism in vivo
Nature Immunology, 2002Co-Authors: Ursula Grohmann, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Maria Laura Belladonna, Francesca Fallarino, Filippo Calcinaro, Alberto Falorni, Paola Candeloro, Maria Cristina FiorettiAbstract:Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a critical role in peripheral tolerance. However, regulatory pathways initiated by the interactions of CTLA-4 with B7 counterligands expressed on antigen-presenting cells are not completely understood. We show here that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4-immunoglobulin (CTLA-4-Ig) is contingent upon effective tryptophan Catabolism in the host. In vitro, we show that CTLA-4-Ig regulates cytokine-dependent tryptophan Catabolism in B7-expressing dendritic cells. These data suggest that modulation of tryptophan Catabolism is a means by which CTLA-4 functions in vivo and that CTLA-4 acts as a ligand for B7 receptor molecules that transduce intracellular signals.
Carmine Vacca - One of the best experts on this subject based on the ideXlab platform.
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the combined effects of tryptophan starvation and tryptophan catabolites down regulate t cell receptor ζ chain and induce a regulatory phenotype in naive t cells
Journal of Immunology, 2006Co-Authors: Francesca Fallarino, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Ursula Grohmann, Maria Laura Belladonna, Barbara C Mcgrath, Douglas R Cavener, Claudia Volpi, Pere SantamariaAbstract:Tryptophan Catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan Catabolism affects T cell responses remain unclear. We provide evidence that the short-term, combined effects of tryptophan deprivation and tryptophan catabolites result in GCN2 kinase-dependent down-regulation of the TCR ζ-chain in murine CD8+ T cells. TCR ζ down-regulation can be demonstrated in vivo and is associated with an impaired cytotoxic effector function in vitro. The longer-term effects of tryptophan Catabolism include the emergence of a regulatory phenotype in naive CD4+CD25− T cells via TGF-β induction of the forkhead transcription factor Foxp3. Such converted cells appear to be CD25+, CD69−, CD45RBlow, CD62L+, CTLA-4+, BTLAlow and GITR+, and are capable of effective control of diabetogenic T cells when transferred in vivo. Thus, both tryptophan starvation and tryptophan catabolites contribute to establishing a regulatory environment affecting CD8+ as well as CD4+ T cell function, and not only is tryptophan Catabolism an effector mechanism of tolerance, but it also results in GCN2-dependent generation of autoimmune-preventive regulatory T cells.
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Modulation of tryptophan Catabolism by regulatory T cells
Nature Immunology, 2003Co-Authors: Francesca Fallarino, Ciriana Orabona, Kwang Woo Hwang, Carmine Vacca, Roberta Bianchi, Ursula Grohmann, Maria Laura Belladonna, Maria Cristina Fioretti, Maria-luisa Alegre, Paolo PuccettiAbstract:Regulatory T (T_R) cells manifest constitutive expression of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), but the function of CTLA-4 in mediating the regulatory function of T_R cells is unclear. We show here that mouse CD4^+CD25^+ cells, either resting or induced to overexpress CTLA-4 by treatment with antibody to CD3, initiated tryptophan Catabolism in dendritic cells through a CTLA-4-dependent mechanism. This process required B7 expression and cytokine production by the dendritic cells. In contrast, T_R cells cultured in the presence of bacterial lipopolysaccharide induced tryptophan Catabolism by dendritic cells in a CTLA-4-independent but cytokine-dependent way. Thus, regulation of immunosuppressive tryptophan Catabolism in dendritic cells might represent a major mechanism of action of T_R cells.
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a defect in tryptophan Catabolism impairs tolerance in nonobese diabetic mice
Journal of Experimental Medicine, 2003Co-Authors: Ursula Grohmann, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Maria Cristina Fioretti, Francesca Fallarino, Paolo PuccettiAbstract:The predisposition of nonobese diabetic (NOD) mice to develop autoimmunity reflects deficiencies in both peripheral and central tolerance. Several defects have been described in these mice, among which aberrant antigen-presenting cell function and peroxynitrite formation. Prediabetes and diabetes in NOD mice have been targeted with different outcomes by a variety of immunotherapies, including interferon (IFN)-γ. This cytokine may be instrumental in specific forms of tolerance by virtue of its ability to activate immunosuppressive tryptophan Catabolism. Here, we provide evidence that IFN-γ fails to induce tolerizing properties in dendritic cells from highly susceptible female mice early in prediabetes. This effect is associated with impaired tryptophan Catabolism, is related to transient blockade of the Stat1 pathway of intracellular signaling by IFN-γ, and is caused by peroxynitrite production. However, the use of a peroxynitrite inhibitor can rescue tryptophan Catabolism and tolerance in those mice. This is the first report of an experimental autoimmune disease in which defective tolerance is causally linked to impaired tryptophan Catabolism.
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ctla 4 ig regulates tryptophan Catabolism in vivo
Nature Immunology, 2002Co-Authors: Ursula Grohmann, Ciriana Orabona, Carmine Vacca, Roberta Bianchi, Maria Laura Belladonna, Francesca Fallarino, Filippo Calcinaro, Alberto Falorni, Paola Candeloro, Maria Cristina FiorettiAbstract:Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a critical role in peripheral tolerance. However, regulatory pathways initiated by the interactions of CTLA-4 with B7 counterligands expressed on antigen-presenting cells are not completely understood. We show here that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4-immunoglobulin (CTLA-4-Ig) is contingent upon effective tryptophan Catabolism in the host. In vitro, we show that CTLA-4-Ig regulates cytokine-dependent tryptophan Catabolism in B7-expressing dendritic cells. These data suggest that modulation of tryptophan Catabolism is a means by which CTLA-4 functions in vivo and that CTLA-4 acts as a ligand for B7 receptor molecules that transduce intracellular signals.
