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

Abstract

Abstractγδ 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-γ secretion by human γδ T cells. In addition, ESAT-6 also induces the activation and proliferation of γδ T cells. Phenotypic analysis indicates that IFN-γ–producing γδ 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 γδ T cells from cord blood did not produce IFN-γ in response to ESAT-6. Further studies indicated that stimulation with ESAT-6 directly induced purified γδ T cells to produce IFN-γ, independent of both antigen-presenting cells and CD4+ T cells. Unexpectedly, depletion of CD4+ T cells markedly enhanced IFN-γ production by γδ T cells, indicating that CD4+ T cells regulate the response of γδ T cells. Importantly, CD4+CD25+ T regulatory (Treg) cells but not CD4+CD25− T cells significantly inhibited IFN-γ production by γδ 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 γδ T cells.