title: NFAT2 Regulates Generation of Innate-Like CD8+T Lymphocytes and CD8+T Lymphocytes Responses.
abstract: Nuclear factor of activated T cells (NFAT) 2 null mutant mice diein uteroof cardiac failure, precluding analysis of the role of NFAT2 in lymphocyte responses. Only the NFAT2-/-/Rag-1-/-chimeric mice model gave insight into the role of NFAT2 transcription factor in T lymphocyte development, activation, and differentiation. As reports are mainly focused on the role of NFAT2 in CD4+T lymphocytes activation and differentiation, we decided to investigate NFAT2's impact on CD8+T lymphocyte responses. We report that NFAT2 is phosphorylated and inactive in the cytoplasm of naive CD8+T cells, and upon TCR stimulation, it is dephosphorylated and translocated into the nucleus. To study the role of NFAT2 in CD8+T responses, we employed NFAT2fl/flCD4-Cre mice with NFAT2 deletion specifically in T cells. Interestingly, the absence of NFAT2 in T cells resulted in increased percentage of non-conventional innate-like CD8+T cells. These cells were CD122+, rapid producer of interferon gamma (IFN-γ) and had characteristics of conventional memory CD8+T cells. We also observed an expansion of PLZF+expressing CD3+thymocyte population in the absence of NFAT2 and increased IL-4 production. Furthermore, we found that CD8+T lymphocytes deficient in NFAT2 had reduced activation, proliferation, and IFN-γ and IL-2 production at suboptimal TCR strength. NFAT2 absence did not significantly influence differentiation of CD8+T cells into cytotoxic effector cells but reduced their IFN-γ production. This work documents NFAT2 as a negative regulator of innate-like CD8+T cells development. NFAT2 is required for complete CD8+T cell responses at suboptimal TCR stimulation and regulates IFN-γ production by cytotoxic CD8+T cellsin vitro.
authors.affiliation: Program of Cellular Biology, Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: Emilia
authors.initials: E
authors.lastname: Pachulec
authors.affiliation: Program of Cellular Biology, Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Neitzke-Montinelli
authors.affiliation: Program of Cellular Biology, Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: João P B
authors.initials: JP
authors.lastname: Viola
keywords: CD8+ T lymphocytes; IFN-γ; NFAT2; PLZF; innate-like CD8+ T cells