CD4+ CD25+ Treg cells inhibit human memory gammadelta T cells to produce IFN-gamma in response to M tuberculosis antigen ESAT-6

T cells play an important role in innate immunity against infections; however, the regulation of these cells remains largely unknown. In the present study, we show that ESAT-6, an antigen of Mycobacterium tuberculosis, induces IFN- secretion by human T cells. In addition, ESAT-6 also induces the activation and proliferation of T cells. Phenotypic analysis indicates that IFN-–producing T cells are mainly effector memory cells with the surface phenotype of CD45RA^–CD62L^–CCR7^–. These results were further confirmed by the fact that naive T cells from cord blood did not produce IFN- in response to ESAT-6. Further studies indicated that stimulation with ESAT-6 directly induced purified T cells to produce IFN-, independent of both antigen-presenting cells and CD4⁺ T cells. Unexpectedly, depletion of CD4⁺ T cells markedly enhanced IFN- production by T cells, indicating that CD4⁺ T cells regulate the response of T cells. Importantly, CD4⁺CD25⁺ T regulatory (Treg) cells but not CD4⁺CD25^– T cells significantly inhibited IFN- production by T cells. Taken together, these data demonstrate for the first time that Treg cells can play an important role in the regulation of immune responses of antigen-specific human memory T cells.