The relationship of T-regulatory cell subsets to disease stage, immune activation, and pathogen-specific immunity in HIV infection

BACKGROUND:: Human immunodeficiency virus (HIV) infection is associated with abnormalities in T-regulatory (T-reg) cells, but the effect of HIV on the naive (CD45RO) and memory (CD45RO) CD25CD127CD4 T-reg cell subsets has not been defined. METHODS:: We measured the absolute number and relative percentage of total, naive, and memory T-reg cells in HIV-infected subjects and compared these parameters with their CD4 T cells, viral load, levels of immune activation, and pathogen-specific immunity. RESULTS:: HIV infection was associated with an increased percentage of memory CD25CD127CD4 T-reg cells and a decreased percentage of naive CD25CD127CD4 T-reg cells as CD4 T cells declined. The level of HIV viremia inversely correlated with total, memory, and naive CD25CD127CD4 T-reg cell numbers and percentage of naive CD25CD127CD4 T-reg cells. Lower total, memory, and naive CD25CD127CD4 T-cell numbers were associated with higher levels of immune activation, whereas a higher percentage of CD25CD127CD4 T-reg cells was associated with lower Candida- and HIV-specific immune responses. CONCLUSIONS:: These observations suggest that CD25CD127CD4 T-reg cells contribute to the immunodeficiency seen in HIV disease.