Peripheral CD4 loss of regulatory T cells is associated with persistent viraemia in chronic HIV infection

Chronic HIV infection is associated with T cell abnormalities and altered effector function. Regulatory T cells (T-reg) are CD4(+) T cells that play a critical role in regulating the immune system. The impact of regulatory T cells on HIV infection and disease progression may be highly significant. We hypothesize that chronic antigenic stimulation from a persistent, high viraemic state may promote a population of T-reg that contributes to HIV-associated immune dysfunction. We evaluated the pattern of T-reg in chronically infected, HIV-positive individuals over a course of 6 months. T-reg are depleted at a distinct rate from that of absolute CD4 cells and loss of T-reg is slower in the presence of viral suppression. In vitro depletion of CD25(+) CD4(+) cells resulted in increased Gag-specific CD4 and CD8 responses. A significant correlation between ex vivo measurement of T-reg and Gag-specific CD4 T cell responses was observed (r = -0.41, P = 0.018) with a trend observed with Gag-specific CD8 T cell responses (P = 0.07). The impact of HIV infection on the T-reg population directly complicates the measured effect of T-reg on the immune dysfunction although our data support the important role of T-reg on modulating the effector T cell response in chronic infection.