[HTML][HTML] CD161 expression on mucosa-associated invariant T cells is reduced in HIV-infected subjects undergoing antiretroviral therapy who do not recover CD4+ T …

ML Freeman, SR Morris, MM Lederman - Pathogens & immunity, 2017 - ncbi.nlm.nih.gov
ML Freeman, SR Morris, MM Lederman
Pathogens & immunity, 2017ncbi.nlm.nih.gov
Background: Mucosa-associated invariant T (MAIT) cells are a recently identified class of
innate-like T cells that are involved in the mucosal immune response. MAIT cells are
characterized by expression of TCR Vα7. 2 and CD161. In HIV infection, there is a profound
early loss of MAIT cells from the circulation that never fully recovers, even after prolonged
viral control with antiretroviral therapy (ART). Methods: We analyzed PBMCs from fresh
whole blood from HIV-negative or ART-treated HIV-positive donors with full (Immune …
Abstract
Background:
Mucosa-associated invariant T (MAIT) cells are a recently identified class of innate-like T cells that are involved in the mucosal immune response. MAIT cells are characterized by expression of TCR Vα7. 2 and CD161. In HIV infection, there is a profound early loss of MAIT cells from the circulation that never fully recovers, even after prolonged viral control with antiretroviral therapy (ART).
Methods:
We analyzed PBMCs from fresh whole blood from HIV-negative or ART-treated HIV-positive donors with full (Immune Success) or impaired (Immune Failure) CD4+ T-cell recovery by flow cytometry for T-cell markers, TCR Vα7. 2, and CD161. The PBMCs were cultured with or without TCR-mediated stimulation, and CD161 expression was assessed on Vα7. 2+ T cells. Interferon-γ (IFNγ) production was assessed by intracellular cytokine staining.
Results:
We found a decrease in the percentage of CD3+ T cells that expressed CD161 and the percentage of Vα7. 2+ T cells that expressed CD161, in HIV-infected individuals. We also found a significant increase in the percentage of T cells that were Vα7. 2+ CD161-in immune failure compared to controls, accompanied by an increase in the percentage of Vα7. 2+ CD161-T cells that express CD8+ in donors with immune failure, but not immune success. After TCR stimulation in vitro, Vα7. 2+ T cells reduced expression of CD161, yet Vα7. 2+ CD161-cells from immune failure donors retained the ability to express IFNγ on stimulation.
Conclusions:
Our findings suggest that in immune failure patients, the reduction in peripheral MAIT cells is due, at least in part, to a loss in CD161 expression, and is not merely the result of trafficking into mucosal tissues or cell death. These CD161-cells retain their function.
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