CD8+ Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy

Emily K. Cartwright, Lori Spicer, S. Abigail Smith, David Lee, Randy Fast, Sara Paganini, Benton O. Lawson, Melon Nega, Kirk Easley, Joern E. Schmitz, Steven E. Bosinger, Mirko Paiardini, Ann Chahroudi, Thomas H. Vanderford, Jacob D. Estes, Jeffrey D. Lifson, Cynthia A. Derdeyn, Guido Silvestri

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8–32 week) ART, depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8+ T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.

Original languageEnglish (US)
Pages (from-to)656-668
Number of pages13
JournalImmunity
Volume45
Issue number3
DOIs
StatePublished - Sep 20 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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