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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.
Author Information (click to view)

McGary CS, Deleage C, Harper J, Micci L, Ribeiro SP, Paganini S, Kuri-Cervantes L, Benne C, Ryan ES, Balderas R, Jean S, Easley K, Marconi V, Silvestri G, Estes JD, Sekaly RP, Paiardini M,


McGary CS, Deleage C, Harper J, Micci L, Ribeiro SP, Paganini S, Kuri-Cervantes L, Benne C, Ryan ES, Balderas R, Jean S, Easley K, Marconi V, Silvestri G, Estes JD, Sekaly RP, Paiardini M, (click to view)

McGary CS, Deleage C, Harper J, Micci L, Ribeiro SP, Paganini S, Kuri-Cervantes L, Benne C, Ryan ES, Balderas R, Jean S, Easley K, Marconi V, Silvestri G, Estes JD, Sekaly RP, Paiardini M,

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Immunity 47(4) 776-788.e5 pii 10.1016/j.immuni.2017.09.018

Abstract

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.

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