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

Abstract

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) anti-coagulated 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/T(reg) 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.