Investigating The Balance Between T Helper 17 And Regulatory T Cells In HIV Infection

Acquired immunodeficiency syndrome (AIDS) as an infectious disease which caused by retrovirus HIV-1 has been a great challenge to the global public health and development since its first report in 1981. CD4+ T cell depletion, cell activation and sustained virus infection are three hallmarks of HIV infection. According to the differention and characteristics of CD4+ T cells, they were divided into T helper 1 (Thl) and T helper 2 (Th2), they both play important roles in HIV infection and AIDS disease pathogenesis. The Thl/Th2 paradigm couldn't explain the HIV pathogenesis, more recently, attention has focused on the reciprocal relationship between CD4+T cells secreting interleukin 17 (Th17 cells) and CD4+CD25hi FoxP3+ regulatory T cells (Tregs). Their defferientiation pathways were different from Thl and Th2 cells and becoming the focus in immunology research. In the present study, we characterize Th17, Treg cell frequencies and the relationship between Th17/Treg and disease progression, clarifying the role of the Th17/Treg imbalance in HIV pathogenesis.In this study, we recruited 32 new infected,54 chronic MSM (men who has sex with men) HIV-infected individuals,115 chronic former blood donors (FBD) and 32 healthy donors. Peripheral blood mononuclear cells were isolated from EDTA an ti coagulated fresh whole blood and intracellular cytokines staining and Flowcytometry were used to evaluate the levels of different CD4+ T helper subpopulations Thl7, Treg and their balance. The correlations between these levels and viral loads or CD4 T cell counts respectively, which have been associated with AIDS progression, were also analysed. The effects of Th17, Treg, Th17/Treg on AIDS progression and differences of these levels were further investigated between HIV infected progressors and controllers.Our results indicated that the depletion of Th17 cells were shown in the early stage of HIV infection and restored with the disease progression in the new infection patients. In chronic HIV infected individuals, the level of Th17 cells was stastically decreased. An increased Treg cells was accompanied in the whole stage of HIV infection and correlated with disease progression. Loss of immune-balance between Th17 and Treg were shown during HIV-1 disease progression and closely related to rapid progression of disease. Additionally, we demonstrated that loss of balance between Th17 and Treg is associated with an earlier CD4 T cell decline during the course of HIV infection. Meanwhile, the Th17 levels, Treg levels and Th17/Treg ratios of the Elite Controller group were comparable to those of the HIV-1 negative controls in the follow-up study indicating such an immune-balance in the Elite Controllers may have a critical role in HIV-1 infection.The reciprocal changes in Th17 and Treg levels led to lower Th17/Treg ratios in subjects infected with HIV-1, suggesting a loss of immune-balance in HIV-1 infection which may shed new light into understanding of HIV-1 pathogenesis and regulating mechanisms, facilitating anti-virus drugs development and vaccine evaluation.