HIV-1 Viremia Prevents the Establishment of Interleukin 2–producing HIV-specific Memory CD4+ T Cells Endowed with Proliferative Capacity
Souheil Antoine Younes,Bader Yassine-Diab,Alam R. Dumont,Alam R. Dumont,Mohamed Rachid Boulassel,Zvi Grossman,Jean-Pierre Routy,Rafick Pierre Sekaly,Rafick Pierre Sekaly,Rafick Pierre Sekaly +9 more
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TLDR
The data favor a model whereby competent HIV-specific Tcm continuously arise in small numbers but under persistent antigenemia are rapidly induced to differentiate into IFN-γ only–producing cells that lack self-renewal capacity.Abstract:
CD4+ T cell responses are associated with disease control in chronic viral infections. We analyzed human immunodeficiency virus (HIV)-specific responses in ten aviremic and eight viremic patients treated during primary HIV-1 infection and for up to 6 yr thereafter. Using a highly sensitive 5-(and-6)-carboxyfluorescein diacetate-succinimidyl ester-based proliferation assay, we observed that proliferative Gag and Nef peptide-specific CD4+ T cell responses were 30-fold higher in the aviremic patients. Two subsets of HIV-specific memory CD4+ T cells were identified in aviremic patients, CD45RA- CCR7+ central memory cells (Tcm) producing exclusively interleukin (IL)-2, and CD45RA- CCR7- effector memory cells (Tem) that produced both IL-2 and interferon (IFN)-gamma. In contrast, in viremic, therapy-failing patients, we found significant frequencies of Tem that unexpectedly produced exclusively IFN-gamma. Longitudinal analysis of HIV epitope-specific CD4+ T cells revealed that only cells that had the capacity to produce IL-2 persisted as long-term memory cells. In viremic patients the presence of IFN-gamma-producing cells was restricted to periods of elevated viremia. These findings suggest that long-term CD4+ T cell memory depends on IL-2-producing CD4+ T cells and that IFN-gamma only-producing cells are short lived. Our data favor a model whereby competent HIV-specific Tcm continuously arise in small numbers but under persistent antigenemia are rapidly induced to differentiate into IFN-gamma only-producing cells that lack self-renewal capacity.read more
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HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation
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Constantinos Petrovas,Joseph P. Casazza,Jason M. Brenchley,David Price,Emma Gostick,William C. Adams,Melissa L. Precopio,Timothy W. Schacker,Mario Roederer,Daniel C. Douek,Richard A. Koup +10 more
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References
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TL;DR: In this paper, it was shown that signalling through CD40 can replace CD4+ T-helper cells in priming of helper-dependent CD8+ CTL responses.
Journal ArticleDOI
A conditioned dendritic cell can be a temporal bridge between a CD4 + T-helper and a T-killer cell
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Journal ArticleDOI
Help for cytotoxic-T-cell responses is mediated by CD40 signalling
Sally R.M. Bennett,Sally R.M. Bennett,Francis R. Carbone,Freda Karamalis,Freda Karamalis,Richard A. Flavell,Jacques F. A. P. Miller,William R. Heath +7 more
TL;DR: It is shown that signalling through CD40 on the antigen-presenting cells can replace the requirement for TH cells, indicating that T-cell ‘help’, at least for generation of CTLs by cross-priming, is mediated by signalling throughCD40 onThe antigen- presenting cell.
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.