The Relative Balance between Th17 and Regulatory T cell subsets is Critical for Progression of HIV Infection

Abstract

HIV pathogenesis is extremely complex and involves both immunodeficiency that leads to opportunistic infections and AIDS as well as excessive inflammation and systemic immune activation. Generalized chronic immune activation and the progressive loss of the balance between T-helper 17 (Th17) and T-regulatory (Treg) cells have been demonstrated as leading events in HIV pathogenesis. Recent studies have investigated interactions between Th17 and Treg cells in relation to HIV infection. Th17 cells are perturbed during HIV infection in humans and SIV infection in nonhuman primates. Studies of Th17 cells in humans and nonhuman primates has shown that depletion of these cells is associated with the dissemination of microbial products from the infected gut, increased systemic immune activation, and disease progression. Treg cells, another small sub-population of T-cells involved in preventing or inhibiting autoimmune and inflammatory disorders has also been associated with HIV infection. Treg cells have been associated with the reduced antiviral T-cell responses but not with the suppression of generalized Tcell activation. In HIV patients, a profound depletion of peripheral blood Th17 cells, contrasted with a gradual decline in Treg cells, has also been documented. Both T-cell subsets influence innate immune responses and, in doing so, may shape the progression of HIV infection. Therefore, the relative balance between these two subsets rather than the function of either alone is critical for disease progression following HIV infection. This review provides updates and discussions on the relationship between Th17 and Treg cells subsets and HIV infection and disease progression. Further, the impact of antiretroviral therapy (ART) on these cellular subsets will be reviewed. Finally, unanswered questions relating to Th17/Treg cells and HIV progression and future perspectives for achieving effective therapeutic strategies for HIV infection will be highlighted.