3 years ago

CTLA-4+PD-1− Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques

CTLA-4+PD-1− Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques
Jacob D. Estes, Vincent Marconi, Emily S. Ryan, Kirk Easley, Colleen S. McGary, Leticia Kuri-Cervantes, Luca Micci, Clarisse Benne, Guido Silvestri, Sherrie Jean, Sara Paganini, Mirko Paiardini, Robert Balderas, Susan P. Ribeiro, Rafick-Pierre Sekaly, Justin Harper, Claire Deleage

Summary

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.

Publisher URL: http://www.cell.com/immunity/fulltext/S1074-7613(17)30429-6

DOI: 10.1016/j.immuni.2017.09.018

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