CD4+ CD25+ Treg cells inhibit human memory gammadelta T cells to produce IFN-gamma in response to M tuberculosis antigen ESAT-6.
Gammadelta 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-gamma secretion by human gammadelta T cells. In addition, ESAT-6 also induces the activation and proliferation of gammadelta T cells. Phenotypic analysis indicates that IFN-gamma-producing gammadelta 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 gammadelta T cells from cord blood did not produce IFN-gamma in response to ESAT-6. Further studies indicated that stimulation with ESAT-6 directly induced purified gammadelta T cells to produce IFN-gamma, independent of both antigen-presenting cells and CD4(+) T cells. Unexpectedly, depletion of CD4(+) T cells markedly enhanced IFN-gamma production by gammadelta T cells, indicating that CD4(+) T cells regulate the response of gammadelta T cells. Importantly, CD4(+)CD25(+) T regulatory (Treg) cells but not CD4(+)CD25(-) T cells significantly inhibited IFN-gamma production by gammadelta 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 gammadelta T cells.
Li
Li
L
Department of Immunology, Zhongshan School of Medicine, Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
Wu
Chang-You
CY
D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D014376:Tuberculosis / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015704:CD4 Antigens; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D053645:Interleukin-2 Receptor alpha Subunit; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma