Produção Nacional
Revisado por pares
IFN-γ Production by CD8+ T Cells Depends on NFAT1 Transcription Factor and Regulates Th Differentiation
2005; American Association of Immunologists; Volume: 175; Issue: 9 Linguagem: Inglês
10.4049/jimmunol.175.9.5931
ISSN1550-6606
AutoresLeonardo K. Teixeira, Bruna de Paula Fonseca e Fonseca, Adriana Vieira‐de‐Abreu, Bianca A. Barboza, Bruno Kaufmann Robbs, Patrı́cia T. Bozza, João P. B. Viola,
Tópico(s)T-cell and B-cell Immunology
ResumoAbstract CD8+ T lymphocytes are excellent sources of IFN-γ; however, the molecular mechanisms that dictate IFN-γ 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-γ 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-γ upon primary T cell activation, and also that the IFN-γ produced by naive CD8+ T cells may enhance CD4+ Th1 differentiation in vitro. TCR stimulation rapidly induced IFN-γ 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-γ gene promoter, and induce IFN-γ production. In fact, NFAT1-deficient mice demonstrated highly impaired IFN-γ production by naive CD8+ T lymphocytes, which were totally rescued after retroviral transduction with NFAT1-encoding vectors. Moreover, NFAT1-dependent IFN-γ production by the CD8+ T cell compartment was crucial to control a Th2-related response in vivo, such as allergic inflammation. Consistently, CD8α- as well as IFN-γ-deficient mice did not mount a Th1 immune response and also developed in vivo allergic inflammation. Our results clearly indicate that IFN-γ production by CD8+ T cells is dependent of NFAT1 transcription factor and may be an essential regulator of Th immune responses in vivo.
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