The Relationship of T-Regulatory Cell Subsets to Disease Stage, Immune Activation, and Pathogen-Specific Immunity in HIV Infection

Abstract

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) CD25+CD127loCD4+ T-reg cell subsets has not been defined. 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. HIV infection was associated with an increased percentage of memory CD25+CD127loCD4+ T-reg cells and a decreased percentage of naive CD25+CD127loCD4+ T-reg cells as CD4+ T cells declined. The level of HIV viremia inversely correlated with total, memory, and naive CD25+CD127loCD4+ T-reg cell numbers and percentage of naive CD25+CD127loCD4+ T-reg cells. Lower total, memory, and naive CD25+CD127loCD4+ T-cell numbers were associated with higher levels of immune activation, whereas a higher percentage of CD25+CD127loCD4+ T-reg cells was associated with lower Candida- and HIV-specific immune responses. These observations suggest that CD25+CD127loCD4+ T-reg cells contribute to the immunodeficiency seen in HIV disease.