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

Colleen S. McGary, Claire Deleage, Justin Harper, Luca Micci, Susan P. Ribeiro, Sara Paganini, Leticia Kuri-Cervantes, Clarisse Benne, Emily S. Ryan, Robert Balderas, Sherrie Jean, Kirk Easley, Vincent Marconi, Guido Silvestri, Jacob D. Estes, Rafick Pierre Sekaly, Mirko Paiardini

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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. 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.

Original languageEnglish (US)
Pages (from-to)776-788.e5
JournalImmunity
Volume47
Issue number4
DOIs
StatePublished - Oct 17 2017

Keywords

  • CTLA-4
  • HIV
  • PD-1
  • SIV
  • T follicular helper cells
  • animal models
  • co-inhibitory receptors
  • latent viral reservoir
  • regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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