CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4 T Cells.

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 Vα7.2CD161- in immune failure compared to controls, accompanied by an increase in the percentage of Vα7.2CD161- 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 Vα7.2CD161- 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.