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

Summary 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.