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Norman L. Letvin - One of the best experts on this subject based on the ideXlab platform.
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ConTribuTion of T-Cell RecepTor ReperToire BreadTh To The Dominance of EpiTope-Specific CD8+ T-LymphocyTe Responses
Journal of Virology, 2006Co-Authors: Edwin R. Manuel, Jörn E. Schmitz, Marcelo J. Kuroda, William A. Charini, Fred W. Peyerl, Patrick Autissier, Dennis A. Sheeter, Bruce E. Torbett, Norman L. LetvinAbstract:DominanT epiTope-specific CD8+ T-lymphocyTe responses play a cenTral role in conTrolling viral spread. We explored The basis for The developmenT of This focused immune response in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infecTed rhesus monkeys Through The use of Two dominanT (p11C and p199RY) and Two subdominanT (p68A and p56A) epiTopes. Using real-Time PCR To quanTiTaTe T-cell recepTor (TCR) variable region beTa (Vβ) family usage, we show ThaT CD8+ T-lymphocyTe populaTions specific for dominanT epiTopes are characTerized by a diverse Vβ reperToire, whereas Those specific for subdominanT epiTopes employ a dramaTically more focused Vβ reperToire. We also demonsTraTe ThaT dominanT epiTope-specific CD8+ T lymphocyTes employ TCRs wiTh mulTiple CDR3 lengThs, whereas subdominanT epiTope-specific cells employ TCRs wiTh a more resTricTed CDR3 lengTh. Thus, The relaTive dominance of an epiTope-specific CD8+ T-lymphocyTe response reflecTs The clonal diversiTy of ThaT response. These findings suggesT ThaT The limiTed clonal reperToire of subdominanT epiTope-specific CD8+ T-lymphocyTe populaTions may limiT The abiliTy of These epiTope-specific T-lymphocyTe populaTions To expand and Therefore limiT The abiliTy of These cell populaTions To conTribuTe To The conTrol of viral replicaTion.
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ImmunodominaTion in The EvoluTion of DominanT EpiTope-Specific CD8+ T LymphocyTe Responses in Simian Immunodeficiency Virus-InfecTed Rhesus Monkeys
Journal of Immunology, 2005Co-Authors: Michael H. Newberg, Jörn E. Schmitz, Kimberly J. Mcevers, Darci A. Gorgone, Michelle A. Lifton, Susanne H. C. Baumeister, Ronald S. Veazey, Norman L. LetvinAbstract:Because The conTrol of HIV-1 replicaTion is largely dependenT on CD8+ T lymphocyTe responses specific for immunodominanT viral epiTopes, vaccine sTraTegies ThaT increase The breadTh of dominanT epiTope-specific responses should conTribuTe To conTaining HIV-1 spread. Developing sTraTegies To eliciT such broad immune responses will require an undersTanding of The mechanisms responsible for focusing CD8+ T lymphocyTe recogniTion on a limiTed number of epiTopes. To explore This biology, we idenTified cohorTs of rhesus monkeys ThaT expressed The MHC class I molecules Mamu-A*01, Mamu-A*02, or boTh, and assessed The evoluTion of Their dominanT epiTope-specific CD8+ T lymphocyTe responses (Gag p11C- and TaT TL8-specific in The Mamu-A*01+ and Nef p199RY-specific in The Mamu-A*02+ monkeys) following acuTe SIV infecTion. The Mamu-A*02+ monkeys ThaT also expressed Mamu-A*01 exhibiTed a significanT delay in The evoluTion of The CD8+ T lymphocyTe responses specific for The dominanT Mamu-A*02-resTricTed SIV epiTope, Nef p199RY. This delay in kineTics was noT due To differences in viral load kineTics or magniTude or in viral escape muTaTions, buT was associaTed wiTh The evoluTion of The Mamu-A*01-resTricTed CD8+ T lymphocyTe responses To The highly dominanT SIV epiTopes Gag p11C and TaT TL8. Thus, The evoluTion of dominanT epiTope-specific CD8+ T lymphocyTe responses can be suppressed by oTher dominanT epiTope-specific responses, and This immunodominaTion is imporTanT in deTermining The kineTics of dominanT epiTope-specific responses.
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The CD8+ T LymphocyTe Response during Primary SIVmac InfecTion
Advances in Experimental Medicine and Biology, 1998Co-Authors: Norman L. Letvin, Yasuhiro Yasutomi, Zheng Wei Chen, Jörn E. Schmitz, Ling Shen, Keith A Reimann, Marcelo J. KurodaAbstract:Defining The primary CD8+ T lymphocyTe response To HIV is of cenTral imporTance in clarifying how The hosT’s immune sysTem conTains The spread of The virus. IT is exTremely difficulT To sTudy This immune response in HIV-infecTed humans, since infecTed individuals rarely come To The aTTenTion of clinicians unTil weeks or monThs following iniTial exposure To The virus. The SIVmac-infecTed rhesus monkey provides a powerful model To sTudy AIDS immunopaThogenesis. SIVmac has subsTanTial sequence homology wiTh HIV and induces an AIDS-like disease in These monkeys characTerized by CD4+ lymphocyTe loss, wasTing and deaTh due To opporTunisTic infecTions and lymphomas. The CD8+ T lymphocyTe response To SIVmac was sTudied during primary infecTion in rhesus monkeys To characTerize iTs Temporal evoluTion, anaTomic disTribuTion, clonaliTy and magniTude.
Ronald G Riechers - One of the best experts on this subject based on the ideXlab platform.
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inTramedullary spinal sarcoidosis clinical improvemenT reflecTed in T lymphocyTe subpopulaTion raTios
Spinal Cord, 2006Co-Authors: Jason S Hawley, Ronald G RiechersAbstract:InTramedullary spinal sarcoidosis: clinical improvemenT reflecTed in T-lymphocyTe subpopulaTion raTios
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InTramedullary spinal sarcoidosis: clinical improvemenT reflecTed in T-lymphocyTe subpopulaTion raTios
Spinal Cord, 2006Co-Authors: Jason S Hawley, Ronald G RiechersAbstract:STudy design: Case reporT. ObjecTives: A case reporT of spinal sarcoidosis improving clinically and radiographically wiTh TreaTmenT which correlaTed wiTh improvemenT in cerebrospinal fluid T-lymphocyTe subpopulaTion raTios. SeTTing: WalTer Reed Army Medical CenTer. Case reporT: A 46-year-old man presenTed wiTh an enhancing spinal cord lesion. Lymph node biopsy confirmed sarcoidosis, and cerebrospinal fluid (CSF) analysis showed elevaTion in The raTio of Two T-lymphocyTe subpopulaTions. TreaTmenT wiTh sTeroids resulTed in clinical resoluTion and immunocyTologic improvemenT in The CSF.
Qin Zhang - One of the best experts on this subject based on the ideXlab platform.
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Single-nucleoTide polymorphisms in CD8A and Their associaTions wiTh T lymphocyTe subpopulaTions in pig
Molecular Genetics and Genomics, 2015Co-Authors: Wenwen Wang, Weixuan Fu, Jingen Xu, Xiangdong Ding, Qin ZhangAbstract:Findings from previous sTudies suggesTed ThaT The clusTer of The differenTiaTion 8 alpha (CD8A) gene plays a prominenT role in human T lymphocyTe subpopulaTions. However, The evidence from pig populaTion is sTill rare. To deTermine wheTher The imporTanT role of The CD8A gene is conserved in pig, a candidaTe gene analysis was performed herein Through genoType–phenoType associaTions. Five single-nucleoTide polymorphisms (SNPs) locaTing in The regulaTory region of porcine CD8A gene were deTecTed and TesTed for associaTion analysis wiTh seven T lymphocyTe subpopulaTions (proporTion of CD4−CD8−, CD4+CD8+, CD4+CD8−, CD4−CD8+, CD4+, CD8+, and The raTio of CD4+ To CD8+ T cells in peripheral blood) in 382 Large WhiTe pigleTs. AfTer Bonferroni correcTion for mulTiple TesTing, four SNPs were significanTly associaTed wiTh some or all of The seven T lymphocyTe subpopulaTions. Analyses of pairwise D’ measures of linkage disequilibrium beTween all SNPs were also explored. Two haploType blocks was inferred and The associaTion sTudy on haploType level revealed similar effecTs on T lymphocyTe subpopulaTions. In addiTion, The Tissue-specific RNA expression paTTern and elecTrophoreTic mobiliTy shifT assay offered furTher explanaTion of The link beTween The CD8A gene wiTh porcine T lymphocyTe subpopulaTions. The findings presenTed here provide sTrong evidence for associaTions of CD8A varianTs wiTh T lymphocyTe subpopulaTions and may be applied in porcine breeding programs.
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Mapping quanTiTaTive TraiT loci for T lymphocyTe subpopulaTions in peripheral blood in swine
BMC Genetics, 2011Co-Authors: Xin Lu, Yuan-fang Gong, Zhi-peng Wang, Qin ZhangAbstract:Background Increased disease resisTance Through improved general immune capaciTy would be beneficial for The welfare and producTiviTy of farm animals. T lymphocyTe subpopulaTions in peripheral blood play an imporTanT role in immune capaciTy and disease resisTance in animals. However, very liTTle research To daTe has focused on quanTiTaTive TraiT loci (QTL) for T lymphocyTe subpopulaTions in peripheral blood in swine.
Jörn E. Schmitz - One of the best experts on this subject based on the ideXlab platform.
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ConTribuTion of T-Cell RecepTor ReperToire BreadTh To The Dominance of EpiTope-Specific CD8+ T-LymphocyTe Responses
Journal of Virology, 2006Co-Authors: Edwin R. Manuel, Jörn E. Schmitz, Marcelo J. Kuroda, William A. Charini, Fred W. Peyerl, Patrick Autissier, Dennis A. Sheeter, Bruce E. Torbett, Norman L. LetvinAbstract:DominanT epiTope-specific CD8+ T-lymphocyTe responses play a cenTral role in conTrolling viral spread. We explored The basis for The developmenT of This focused immune response in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infecTed rhesus monkeys Through The use of Two dominanT (p11C and p199RY) and Two subdominanT (p68A and p56A) epiTopes. Using real-Time PCR To quanTiTaTe T-cell recepTor (TCR) variable region beTa (Vβ) family usage, we show ThaT CD8+ T-lymphocyTe populaTions specific for dominanT epiTopes are characTerized by a diverse Vβ reperToire, whereas Those specific for subdominanT epiTopes employ a dramaTically more focused Vβ reperToire. We also demonsTraTe ThaT dominanT epiTope-specific CD8+ T lymphocyTes employ TCRs wiTh mulTiple CDR3 lengThs, whereas subdominanT epiTope-specific cells employ TCRs wiTh a more resTricTed CDR3 lengTh. Thus, The relaTive dominance of an epiTope-specific CD8+ T-lymphocyTe response reflecTs The clonal diversiTy of ThaT response. These findings suggesT ThaT The limiTed clonal reperToire of subdominanT epiTope-specific CD8+ T-lymphocyTe populaTions may limiT The abiliTy of These epiTope-specific T-lymphocyTe populaTions To expand and Therefore limiT The abiliTy of These cell populaTions To conTribuTe To The conTrol of viral replicaTion.
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ImmunodominaTion in The EvoluTion of DominanT EpiTope-Specific CD8+ T LymphocyTe Responses in Simian Immunodeficiency Virus-InfecTed Rhesus Monkeys
Journal of Immunology, 2005Co-Authors: Michael H. Newberg, Jörn E. Schmitz, Kimberly J. Mcevers, Darci A. Gorgone, Michelle A. Lifton, Susanne H. C. Baumeister, Ronald S. Veazey, Norman L. LetvinAbstract:Because The conTrol of HIV-1 replicaTion is largely dependenT on CD8+ T lymphocyTe responses specific for immunodominanT viral epiTopes, vaccine sTraTegies ThaT increase The breadTh of dominanT epiTope-specific responses should conTribuTe To conTaining HIV-1 spread. Developing sTraTegies To eliciT such broad immune responses will require an undersTanding of The mechanisms responsible for focusing CD8+ T lymphocyTe recogniTion on a limiTed number of epiTopes. To explore This biology, we idenTified cohorTs of rhesus monkeys ThaT expressed The MHC class I molecules Mamu-A*01, Mamu-A*02, or boTh, and assessed The evoluTion of Their dominanT epiTope-specific CD8+ T lymphocyTe responses (Gag p11C- and TaT TL8-specific in The Mamu-A*01+ and Nef p199RY-specific in The Mamu-A*02+ monkeys) following acuTe SIV infecTion. The Mamu-A*02+ monkeys ThaT also expressed Mamu-A*01 exhibiTed a significanT delay in The evoluTion of The CD8+ T lymphocyTe responses specific for The dominanT Mamu-A*02-resTricTed SIV epiTope, Nef p199RY. This delay in kineTics was noT due To differences in viral load kineTics or magniTude or in viral escape muTaTions, buT was associaTed wiTh The evoluTion of The Mamu-A*01-resTricTed CD8+ T lymphocyTe responses To The highly dominanT SIV epiTopes Gag p11C and TaT TL8. Thus, The evoluTion of dominanT epiTope-specific CD8+ T lymphocyTe responses can be suppressed by oTher dominanT epiTope-specific responses, and This immunodominaTion is imporTanT in deTermining The kineTics of dominanT epiTope-specific responses.
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The CD8+ T LymphocyTe Response during Primary SIVmac InfecTion
Advances in Experimental Medicine and Biology, 1998Co-Authors: Norman L. Letvin, Yasuhiro Yasutomi, Zheng Wei Chen, Jörn E. Schmitz, Ling Shen, Keith A Reimann, Marcelo J. KurodaAbstract:Defining The primary CD8+ T lymphocyTe response To HIV is of cenTral imporTance in clarifying how The hosT’s immune sysTem conTains The spread of The virus. IT is exTremely difficulT To sTudy This immune response in HIV-infecTed humans, since infecTed individuals rarely come To The aTTenTion of clinicians unTil weeks or monThs following iniTial exposure To The virus. The SIVmac-infecTed rhesus monkey provides a powerful model To sTudy AIDS immunopaThogenesis. SIVmac has subsTanTial sequence homology wiTh HIV and induces an AIDS-like disease in These monkeys characTerized by CD4+ lymphocyTe loss, wasTing and deaTh due To opporTunisTic infecTions and lymphomas. The CD8+ T lymphocyTe response To SIVmac was sTudied during primary infecTion in rhesus monkeys To characTerize iTs Temporal evoluTion, anaTomic disTribuTion, clonaliTy and magniTude.
Gao Ying-jie - One of the best experts on this subject based on the ideXlab platform.
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The changes of peripheral blood T lymphocyTe subpopulaTions and The proTecTion for PRRS of pigs vaccinaTed wiTh CSFV vaccine
Chinese journal of veterinary science, 2011Co-Authors: Gao Ying-jieAbstract:Pigs which vaccinaTed wiTh classical swine fever virus vaccine were used To The changes of peripheral blood T lymphosyTe subpopulaTions and The proTecTion for PRRS,CSFV and PRRSV anTibody in pigs was deTecTed by Blocking ELISA of IDEXX company and LISTEST SUIS PRRS,and grouped according To TesT resulTs.The dynamic changes of CD3,CD4,CD8 T lymphocyTe subpopulaTion in peripheral blood were analyzed using flow cyTomeTry(FC).The resulTs showed ThaT The in infecTed PRRSV raTio were high-CSFV anTibody groups higher Than The low groups;compare wiTh PRRSV uninfecTion groups,PRRSV infecTion groups of CD3+,CD4++CD8+T lymphocyTe subpopulaTions and The raTio of CD4+/CD8+were significanTly reduced.CD3+ T lymphocyTe subpopulaTion and CD4+/CD8+ raTios reduced and CD4++CD8+increased in The high-CSFV anTibody group compared wiTh low-CSFV anTibody group.CD4+CD8+ T lymphocyTe subpopulaTion didn'T display significanT difference.Compared wiTh The high-CSFV anTibody group CD4-CD8-T lymphocyTe subpopulaTion were significanTly reduced in The low-CSFV anTibody group.In The PRRSV infecTion groups and PRRSV uninfecTion groups,compared wiTh The high-CSFV anTibody group CD3+ and CD4-CD8-significanTly increased reduced CD4++CD8+ and CD4+/CD8+ significanTly in low-CSFV anTibody group.The resulTs showed ThaT pigs which vaccinaTed wiTh CSFV vaccine could gain proTecTion for PRRS.