Immune exhaustion occurs concomitantly with immune activation and decrease in regulatory T cells in viremic chronically HIV-1-infected patients

Meenakshi Sachdeva, Margaret A. Fischl, Rajendra Pahwa, Naresh Sachdeva, Savita Pahwa

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Background: Chronic HIV-1 infection is associated with excessive immune activation and immune exhaustion. We investigated the relationship of these 2 phenotypes and frequency of regulatory T cells (Tregs) in controlled and uncontrolled chronic HIV-1 infection. Methods: Immune exhaustion marker PD-1, its ligand PD-L1, CD4+CD25bright FoxP3+ Tregs, HLA-DR, and CD38 coexpression as activation markers were investigated in peripheral blood lymphocytes of 44 HIV-1-infected patients and 11 HIV-1-uninfected controls by multicolor flow cytometry. Results: Activated and PD-1 expressing T cells were increased, and Tregs were decreased in HIV-1-infected patients as compared with controls, and alterations were greatest in viremic patients. The proportion of activated CD8+ T cells exceeded activated CD4+ T cells. Tregs had an inverse correlation with activated T cells and PD-1 expressing T cells. PD-L1 was highly expressed on monocytes and to a lesser extent on T lymphocytes of patients. These abnormalities partially reversed with virologic control after potent antiretroviral therapy. Conclusions: Immune exhaustion is a component of aberrant immune activation in chronic HIV-1 infection and is associated with loss of Tregs and ongoing virus replication. These defects are corrected partially with effective virologic control by potent antiretroviral therapy.

Original languageEnglish (US)
Pages (from-to)447-454
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume54
Issue number5
DOIs
StatePublished - Aug 15 2010

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Keywords

  • ART
  • CD8
  • HIV-1
  • immune activation
  • immune exhaustion
  • T cells

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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