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

J Acquir Immune Defic Syndr. 2010 Aug;54(5):447-54. doi: 10.1097/QAI.0b013e3181e0c7d0.


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, CD4CD25 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • Chronic Disease
  • Female
  • Flow Cytometry
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Lymphocyte Activation*
  • Male
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology*


  • Antigens, CD