In Human Immunodeficiency Virus primary infection, early combined antiretroviral therapy reduced γδ T‐cell activation but failed to restore their polyfunctionality. Issue 4 (8th July 2019) - Casetti, Rita
Summary: Primary and chronic human immunodeficiency virus (HIV) infection alters γδ T‐cell features. However, there is no evidence about early combined antiretroviral therapy (cART) and γδ T‐cell dynamics. In the present study, HIV‐positive individuals were divided into those with early primary infection (EPI) and those with late primary infection (LPI). The analysis of γδ T cells was performed by flow cytometry before and after therapy. Polyfunctional profile was assessed after in vitro peripheral blood mononuclear cell (PBMC) exposure to specific antigens. The results show that primary infection induced an expansion of V δ 1 T cells in LPI. Before treatment, a massive activation of γδ T‐cell subsets was observed in both groups of patients, that correlated with disease progression and was significantly reduced after cART introduction. Despite this, CD107A‐expressing V δ 1 T cells in both groups were significantly fewer than in healthy donors, but were restored by therapy introduction. Polyfunctional analysis of V δ 1 T cells from HIV‐positive individuals revealed a lower frequency of CD107A + CCL‐4 + V δ 1 T‐cell subsets than healthy donors that persists after therapy. Functional profile of V δ 2 was similar to that in healthy donors before therapy but, at 6 months, a lower frequency of CD107A, interferon‐ γ ‐ or tumor necrosis factor‐ α ‐producing V δ 2 T cells was observed in the EPI group. Finally, individuals with LPI showed a lower frequency of quadruple‐functional V δ 2 T‐cell subset. In conclusion, during primary HIV infection, the baseline V δ 1 T‐cell activation is correlated with immune reconstitution potential. Moreover, an altered γδ polyfunctional profile occurred, persisting after cART. Further studies are needed to understand whether a longer treatment of primary infection may increase γδ T‐cell functionality. Abstract : Combined antiretroviral therapy reduces γδ T‐cell activation but fails to restore polyfunctionality.