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

P>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+ CD25highCD127lowforkhead box P3 (FoxP3high)] 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 center dot 403, P < 0 center dot 0001). The proportion of T-regs also correlated positively with HIV-1 plasmaviraemia (r = 0 center dot 323, P = 0 center dot 002), but correlated inversely with CD4+ cells (r = -0 center dot 312, P = 0 center dot 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 center dot 305, P = 0 center dot 005), and the percentage of T-regs tended to correlate with HIV-1 DNA load (r = 0 center dot 224, P = 0 center dot 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.