Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy
Graham S. Ogg,Xia Jin,Sebastian Bonhoeffer,Paul Moss,Martin A. Nowak,Simon Monard,Jeremy P. Segal,Yunzhen Cao,Sarah Rowland-Jones,Arlene Hurley,M. Markowitz,David D. Ho,Andrew J. McMichael,Douglas F. Nixon +13 more
TLDR
Using HLA/peptide tetrameric complexes, it is shown that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks, followed by an exponential decay which continues while viremia remains undetectable.Abstract:
Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days) of HIV-1-specific CTL which continues while viremia remains undetectable. These data have implications for the immunological control of drug-resistant virus.read more
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HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors.
Stephen A. Migueles,M. Shirin Sabbaghian,W. Lesley Shupert,Maria P. Bettinotti,Francesco M. Marincola,Lisa Martino,Clair W. Hallahan,Sara Selig,David C. Schwartz,John S. Sullivan,Mark Connors +10 more
TL;DR: These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease and strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule.
Journal ArticleDOI
HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors
Stephen A. Migueles,Alisha C. Laborico,W. Lesley Shupert,M. Shirin Sabbaghian,Ronald L. Rabin,Claire W. Hallahan,Debbie van Baarle,Stefan Kostense,Frank Miedema,Mary McLaughlin,Linda A. Ehler,Julia A. Metcalf,Shuying Liu,Mark Connors +13 more
TL;DR: Results indicated that nonprogressors were differentiated by increased proliferative capacity of HIV-specific CD8+ T cells linked to enhanced effector function, and the relative absence of these functions in progressors may represent a mechanism by which HIV avoids immunological control.
Journal ArticleDOI
HIV-Specific Cd8+T Cells Produce Antiviral Cytokines but Are Impaired in Cytolytic Function
Victor Appay,Douglas F. Nixon,Sean M. Donahoe,Geraldine M. Gillespie,Tao Dong,Abigail S. King,Graham S. Ogg,Hans M. L. Spiegel,Christopher P. Conlon,Celsa A. Spina,Celsa A. Spina,Diane V. Havlir,Douglas D. Richman,Douglas D. Richman,Anele Waters,Philippa J. Easterbrook,Andrew J. McMichael,Sarah Rowland-Jones +17 more
TL;DR: The majority of circulating CD8+ T cells specific for CMV and HIV antigens are functionally active with regards to the secretion of antiviral cytokines in response to antigen, although a subset of tetramer-staining cells was identified that secretes IFN-γ and MIP-1β but not TNF-α.
Journal ArticleDOI
Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level
Corey Moore,Mina John,Ian James,Frank T. Christiansen,Frank T. Christiansen,Campbell S. Witt,Simon Mallal +6 more
TL;DR: A fundamental role is supported for HLA-restricted immune responses in driving and shaping HIV-1 evolution in vivo and at a population level the degree of HLA–associated selection in viral sequence was predictive of viral load.
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Analysis of total human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T-cell responses: relationship to viral load in untreated HIV infection
Michael R. Betts,David R. Ambrozak,Daniel C. Douek,Sebastian Bonhoeffer,Jason M. Brenchley,Joseph P. Casazza,Richard A. Koup,Louis J. Picker +7 more
TL;DR: Overall frequencies of HIV-specific T cells are not the sole determinant of immune-mediated protection in HIV-infection, and a positive correlation was identified between the plasma viral load and the total HIV-, Env-, and Nef-specific CD8+ T-cell frequency.
References
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Phenotypic Analysis of Antigen-Specific T Lymphocytes
John D. Altman,Paul Moss,Philip J. R. Goulder,Dan H. Barouch,Michael G. McHeyzer-Williams,John I. Bell,Andrew J. McMichael,Mark M. Davis +7 more
TL;DR: Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals and correlated well with cytotoxicity assays.
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Kaja Murali-Krishna,John D. Altman,M. Suresh,David J. D. Sourdive,Allan J. Zajac,Joseph D. Miller,Jill E. Slansky,Rafi Ahmed +7 more
TL;DR: Much of the CD8 T cell expansion seen during viral infection represents antigen-specific cells and warrants a revision of current thinking on the size of the antiviral response.
Journal ArticleDOI
Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia
Eric S. Rosenberg,James M. Billingsley,Angela M. Caliendo,Steven L. Boswell,Paul E. Sax,Spyros A. Kalams,Bruce D. Walker +6 more
TL;DR: In individuals who control viremia in the absence of antiviral therapy, polyclonal, persistent, and vigorous HIV-1-specific CD4+ T cell proliferative responses were present, resulting in the elaboration of interferon-gamma and antiviral beta chemokines.
Journal ArticleDOI
Positive Effects of Combined Antiretroviral Therapy on CD4+ T Cell Homeostasis and Function in Advanced HIV Disease
Brigitte Autran,Guislaine Carcelain,T.S. Li,Catherine Blanc,Dominique Mathez,R. Tubiana,C. Katlama,Patrice Debré,Jacques Leibowitch +8 more
TL;DR: In this article, a three-phase T cell reconstitution was demonstrated after HAART, with an early rise of memory CD4(+) cells, a reduction in T cell activation correlated to the decreasing retroviral activity together with an improved CD4+ T cell reactivity to recall antigens.
Journal ArticleDOI
Immunological Memory and Protective Immunity: Understanding Their Relation
Rafi Ahmed,David Gray +1 more
TL;DR: The current understanding of the cellular basis of immune memory is reviewed and the relative contributions made to protective immunity by memory and effector T and B cells are examined.