Loss of balance between T helper type 17 and regulatory T cells in chronic human immunodeficiency virus infection

The aim of this study is to characterize the changes of CD4(+)CD25(high)forkhead box P3 (FoxP3(+)) regulatory T cells (T-reg), interleukin (IL)-17 secreting T helper type 17 (Th17) cell frequencies and the balance of these two subsets in a cohort of chronic human immunodeficiency virus type 1 (HIV-1)-infected patients in China. A total of 115 untreated chronic HIV-infected individuals and 32 healthy donors were recruited in this study. Peripheral blood mononuclear cells were isolated from ethylenediamine tetracetic acid (EDTA) anticoagulated fresh whole blood and stained to characterize the frequencies of T-reg and Th17. Of a total 115 patients, 42 individuals including 10 elite controllers were followed-up for more than 1 year, and changes of T-reg and Th17 frequencies were analysed over time. The continuous loss of Th17 cells was accompanied by a concomitant rise in the frequency of T-reg cells, resulting in a loss of Th17/T-reg balance during the progressive HIV infection. Meanwhile, the T-reg levels, Th17 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. Additionally, we demonstrated that loss of balance between Th17 and T-reg is associated with an earlier CD4 T cell decline during the course of HIV infection. Our results indicate that a loss of immune-balance of Th17 to T-reg during HIV-1 disease progression and the persistence of such an immune-balance in the elite controllers may have a critical role in HIV-1 infection and further shed new light into understanding the pathogenesis of HIV-1.