Increased frequency of CD4(+)CD25(high) Treg cells inhibit BCG-specific induction of IFN-gamma by CD4(+) T cells from TB patients

Abstract

Cell-mediated immunity plays a considerable role in the protection against Mycobacterium tuberculosis infection. The immune response to tuberculosis (TB) was dominated by both CD4(+) T cells with the T helper 1 type cytokines and CD8(+) T cells. Recent studies have suggested that the circumstances in which protective or tissue-damaging T cell responses to microbes are affected by the activity of Treg (CD4(+)CD25(high)) cells. In the present study, we demonstrated that the frequencies of CD4(+)CD25(+) and CD4(+)CD25(high) T cells in TB patients were significantly higher compared to normal individuals. These Treg cells expressed CTLA-4 and Foxp3 at protein level and displayed activation and memory phenotypes as assessed by flow cytometric analysis. The frequencies of CD4(+)CD25(high)CTLA-4(+) and CD4(+)CD25(high)Foxp3(+) T cells within the total CD4(+) T cell population were significantly increased in the blood of TB patients compared to healthy donors. Moreover, the expression of GITR on Treg cells was higher in TB patients than in normal donors. The phenotypic analysis demonstrated that CD4(+)CD25(high) Treg expressed higher levels of CD45RO and HLA-DR, and lower levels of CD45RA compared to CD4(+)CD25(low) and CD4(+)CD25(-) T cells. The addition of CD4(+)CD25(high) T cells back to cultures could significantly suppress the antigen-specific production of IFN-gamma induced by BCG-stimulated CD4(+)CD25(-) T cells, suggesting that Treg might play a key role in the control of cellular immune responses in TB infection.