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

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 54; no. 5; p. 447
• Main Authors: Sachdeva, Meenakshi, Fischl, Margaret A, Pahwa, Rajendra, Sachdeva, Naresh, Pahwa, Savita
• Format: Journal Article
• Language: English
• Published: United States 15.08.2010
• Subjects: 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
• ISSN: 1944-7884
• DOI: 10.1097/QAI.0b013e3181e0c7d0

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. 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. 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. 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.