TY - JOUR
T1 - CTLA-4+PD-1− Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques
AU - McGary, Colleen S.
AU - Deleage, Claire
AU - Harper, Justin
AU - Micci, Luca
AU - Ribeiro, Susan P.
AU - Paganini, Sara
AU - Kuri-Cervantes, Leticia
AU - Benne, Clarisse
AU - Ryan, Emily S.
AU - Balderas, Robert
AU - Jean, Sherrie
AU - Easley, Kirk
AU - Marconi, Vincent
AU - Silvestri, Guido
AU - Estes, Jacob D.
AU - Sekaly, Rafick Pierre
AU - Paiardini, Mirko
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/10/17
Y1 - 2017/10/17
N2 - Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1+ follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4+PD-1− memory CD4+ T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus. In contrast to PD-1+ Tfh cells, SIV-enriched CTLA-4+PD-1− CD4+ T cells were found outside the B cell follicle of the LN, predicted the size of the persistent viral reservoir during ART, and significantly increased their contribution to the SIV reservoir with prolonged ART-mediated viral suppression. We have shown that CTLA-4+PD-1− memory CD4+ T cells are a previously unrecognized component of the SIV and HIV reservoir that should be therapeutically targeted for a functional HIV-1 cure. HIV persists in T follicular helper cells within the lymph node during antiretroviral therapy, but decays with time. McGary et al. identify the persistence of replication-competent SIV and HIV outside the lymph node follicle in a unique subset of CTLA-4+PD-1− memory CD4+ T cells that share features with regulatory T cells.
AB - Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1+ follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4+PD-1− memory CD4+ T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus. In contrast to PD-1+ Tfh cells, SIV-enriched CTLA-4+PD-1− CD4+ T cells were found outside the B cell follicle of the LN, predicted the size of the persistent viral reservoir during ART, and significantly increased their contribution to the SIV reservoir with prolonged ART-mediated viral suppression. We have shown that CTLA-4+PD-1− memory CD4+ T cells are a previously unrecognized component of the SIV and HIV reservoir that should be therapeutically targeted for a functional HIV-1 cure. HIV persists in T follicular helper cells within the lymph node during antiretroviral therapy, but decays with time. McGary et al. identify the persistence of replication-competent SIV and HIV outside the lymph node follicle in a unique subset of CTLA-4+PD-1− memory CD4+ T cells that share features with regulatory T cells.
KW - CTLA-4
KW - HIV
KW - PD-1
KW - SIV
KW - T follicular helper cells
KW - animal models
KW - co-inhibitory receptors
KW - latent viral reservoir
KW - regulatory T cells
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U2 - 10.1016/j.immuni.2017.09.018
DO - 10.1016/j.immuni.2017.09.018
M3 - Article
C2 - 29045906
AN - SCOPUS:85032836283
SN - 1074-7613
VL - 47
SP - 776-788.e5
JO - Immunity
JF - Immunity
IS - 4
ER -