Increased Turnover of FoxP3high Regulatory T Cells Is Associated With Hyperactivation and Disease Progression of Chronic HIV-1 Infection

Objectives: To characterize the homeostasis of CD4(+)FoxP3(high) regulatory T cells (Treg) and its association with immune hyperactivation in the disease progression of chronic HIV-1 infection. Design: Treg proliferation and apoptosis markers were determined and the relation to disease progression and Treg activation was analyzed. Methods: Fifty-six HIV-1-infected highly active antiretroviral therapy (HAART)-naive subjects and 17 HAART-treated subjects were enrolled. Proliferation and apoptosis of Treg from peripheral blood were evaluated by intracellular Ki-67 and active caspase-3 or surface Annexin-V staining. T-cell activation markers, CD38 and HLA-DR, were simultaneously monitored. The effects of in vitro TCR (T cell receptor) stimulation on proliferation, apoptosis, and activation of Treg were determined from both HIV-1-infected subjects and healthy controls. Results: HIV-1-infected patients displayed increased Treg turnover status indicated by higher expression of proliferation marker Ki-67 and apoptosis marker active caspase-3 and Annexin-V. Turnover level of Treg was positively associated with disease progression and immune hyperactivation. In vitro TCR stimulation increased the turnover level of Treg. The HAART treatment decreased the turnover and activation levels of Treg in complete responders. Conclusions: Turnover level of Treg was increased in HIV-1-infected subjects, which is associated with immune hyperactivation and the disease progression, and may serve as a surrogate marker to predict HIV-1 disease progression.