Article
IFN-gamma production by CD8+ T cells depends on NFAT1 transcription factor and regulates Th differentiation
Registro en:
TEIXEIRA, Leonardo K. et al. IFN- Production by CD8 T Cells Depends on NFAT1 Transcription Factor and Regulates Th Differentiation. Journal of Immunology, v. 175, p. 5931-5939, 2005.
0022-1767
10.4049/jimmunol.175.9.5931
1550-6606
Autor
Teixeira, Leonardo K.
Fonseca, Bruna P. F.
Abreu, Adriana Vieira de
Barboza, Bianca A.
Robbs, Bruno K.
Bozza, Patrícia T.
Viola, João P. B.
Resumen
CD8+ T lymphocytes are excellent sources of IFN-gamma; however, the molecular mechanisms that dictate IFN-gamma expression upon TCR stimulation in these cells are not completely understood. In this study, we evaluated the involvement of NFAT1 in the regulation of IFN-gamma gene expression in murine CD8+ T cells and its relevance during Th differentiation. We show that CD8+, but not CD4+, T cells, represent the very first source of IFN-gamma upon primary T cell activation, and also that the IFN-gamma produced by naive CD8+ T cells may enhance CD4+ Th1 differentiation in vitro. TCR stimulation rapidly induced IFN-gamma expression in CD8+ T lymphocytes in a cyclosporin A-sensitive manner. Evaluation of CD8+ T cells showed that calcium influx alone was sufficient to activate NFAT1 protein, transactivate IFN-gamma gene promoter, and induce IFN-gamma production. In fact, NFAT1-deficient mice demonstrated highly impaired IFN-gamma production by naive CD8+ T lymphocytes, which were totally rescued after retroviral transduction with NFAT1-encoding vectors. Moreover, NFAT1-dependent IFN-gamma production by the CD8+ T cell compartment was crucial to control a Th2-related response in vivo, such as allergic inflammation. Consistently, CD8alpha- as well as IFN-gamma-deficient mice did not mount a Th1 immune response and also developed in vivo allergic inflammation. Our results clearly indicate that IFN-gamma production by CD8+ T cells is dependent of NFAT1 transcription factor and may be an essential regulator of Th immune responses in vivo.