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 Estes, Rafick Pierre Sekaly, Mirko Paiardini

Research output: Contribution to journalArticle

47 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.

Original languageEnglish (US)
Pages (from-to)776-788
Number of pages13
JournalImmunity
Volume47
Issue number4
DOIs
StatePublished - Oct 17 2017
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    McGary, C. S., Deleage, C., Harper, J., Micci, L., Ribeiro, S. P., Paganini, S., Kuri-Cervantes, L., Benne, C., Ryan, E. S., Balderas, R., Jean, S., Easley, K., Marconi, V., Silvestri, G., Estes, J., Sekaly, R. P., & Paiardini, M. (2017). CTLA-4+PD-1- Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques. Immunity, 47(4), 776-788. https://doi.org/10.1016/j.immuni.2017.09.018