Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV‐1)‐infected children

Summary The function of CD4 + T cells with regulatory activity (T regs ) is the down‐regulation of immune responses. This suppressive activity may limit the magnitude of effector responses, resulting in failure to control human immunodeficiency virus 1 (HIV‐1) infection, but may also suppress chronic immune activation, a characteristic feature of HIV‐1 disease. We evaluated the correlation between viral load, immune activation and T regs in HIV‐1‐infected children. Eighty‐nine HIV‐1‐infected children (aged 6–14 years) were included in the study and analysed for HIV‐1 plasmaviraemia, HIV‐1 DNA load, CD4 and CD8 cell subsets. T reg cells [CD4 + CD25 high CD127 low forkhead box P3 (FoxP3 high )] and CD8‐activated T cells (CD8 + CD38 + ) were determined by flow cytometry. Results showed that the number of activated CD8 + CD38 + T cells increased in relation to HIV‐1 RNA plasmaviraemia ( r  = 0·403, P  < 0·0001). The proportion of T regs also correlated positively with HIV‐1 plasmaviraemia ( r  = 0·323, P  = 0·002), but correlated inversely with CD4 + cells ( r  = −0·312, P  = 0·004), thus suggesting a selective expansion along with increased viraemia and CD4 + depletion. Interestingly, a positive correlation was found between the levels of T regs and CD8 + CD38 + T cells ( r  = 0·305, P  = 0·005), and the percentage of T regs tended to correlate with HIV‐1 DNA load ( r  = 0·224, P  = 0·062). Overall, these findings suggest that immune activation contributes to the expansion of T reg cells. In turn, the suppressive activity of T regs may impair effector responses against HIV‐1, but appears to be ineffective in limiting immune activation.