Immune exhaustion occurs concomitantly with immune activation and decrease in regulatory T cells in viremic chronically HIV-1-infected patients.
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.
Sachdeva
Meenakshi
M
Department of Microbiology and Immunology, Developmental Center for AIDS Research, University of Miami-Miller School of Medicine, Miami, FL 33136, USA.
Fischl
Margaret A
MA
Pahwa
Rajendra
R
Sachdeva
Naresh
N
Pahwa
Savita
S
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015703:Antigens, CD
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