Lymphocyte activation gene-3 expression defines a discrete subset of HIV-Specific CD8⁺ T cells that is associated with Lower Viral Load

Mechanisms leading to the observed immune dysregulation in chronic HIV infection are not well understood. The MHC-II class ligand, lymphocyte activation gene-3 (LAG-3, CD223), has been implicated in the complex regulation mechanism of immune functions. In this study, we describe a new population of HIV-specific CD8⁺ T cells expressing LAG-3. These LAG-3 ⁺CD8⁺ T cells do not display immunophenotypic patterns traditionally attributed to regulatory T cells. The LAG3⁺CD8 ⁺ T cells are CCR7⁺,CD127^-, and display heterogeneous surface expressions of CD45RA and CD25. Interestingly, HIV-specific LAG-3⁺CD8⁺ T cells do not substantially express CTLA-4 and LAG-3 expression does not correlate with interleukin (IL)-10 or tumor growth factor (TGF)-β production. In addition, HIV-specific LAG3⁺CD8⁺ T cells do not produce interferon (IFN-γ) or express CD107a. The frequency of HIV-specific LAG3⁺CD8⁺ T cells negative correlated with plasma viral load. Our study introduces a new population of HIV-specific CD8⁺ T cells and proposes additional mechanisms of immune regulation in chronic HIV infection.