IFN-gamma production by CD8+ T cells depends on NFAT1 transcription factor and regulates Th differentiation

dc.creatorTeixeira, Leonardo K.
dc.creatorFonseca, Bruna P. F.
dc.creatorAbreu, Adriana Vieira de
dc.creatorBarboza, Bianca A.
dc.creatorRobbs, Bruno K.
dc.creatorBozza, Patrícia T.
dc.creatorViola, João P. B.
dc.date2020-04-21T14:09:41Z
dc.date2020-04-21T14:09:41Z
dc.date2005
dc.date.accessioned2023-09-26T20:07:55Z
dc.date.available2023-09-26T20:07:55Z
dc.identifierTEIXEIRA, 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.
dc.identifier0022-1767
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/40903
dc.identifier10.4049/jimmunol.175.9.5931
dc.identifier1550-6606
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8849273
dc.descriptionCD8+ 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Association of Immunologists
dc.rightsopen access
dc.subjectCD8 T Cells
dc.subjectIFN-y
dc.subjectLInfócitos T
dc.subjectCD8 T Cells
dc.subjectIFN-y Production
dc.subjectT lymphocytes
dc.titleIFN-gamma production by CD8+ T cells depends on NFAT1 transcription factor and regulates Th differentiation
dc.typeArticle


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