NFAT2 regulates generation of innate-like CD8+ T lymphocytes and CD8+ T lymphocytes responses
NFAT2 null mutant mice die in utero of 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 ar...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00411/full |
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| author | Emilia Pachulec Vanessa Neitzke-Montinelli Joao P.B. Viola |
| author_facet | Emilia Pachulec Vanessa Neitzke-Montinelli Joao P.B. Viola |
| author_sort | Emilia Pachulec |
| collection | DOAJ |
| description | NFAT2 null mutant mice die in utero of 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 lymphocytes responses. We report that NFAT2 is phosphorylated and inactive in the cytoplasm of naive CD8+ T cells, and upon TCR stimulation 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 nonconventional innate-like CD8+ T cells. These cells were CD122+, rapid producer of IFN-γ and had characteristics of conventional memory CD8+ T cells. We also observed an expansion of PLZF+ expressing CD3+ thymocytes 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 influence significantly differentiation of CD8+ T cells into cytotoxic effector cells, but reduced theirs IFN-γ production. This work documents NFAT2 as a negative regulator of innate-like CD8+ T cells development. NFAT2 is required for a complete CD8+ T cells responses at suboptimal TCR stimulation and regulates IFN-γ production by cytotoxic CD8+ T cells in vitro. |
| first_indexed | 2024-04-12T05:24:56Z |
| format | Article |
| id | doaj.art-a51f157de0f04fcaba276baab1dbe4a7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T05:24:56Z |
| publishDate | 2016-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a51f157de0f04fcaba276baab1dbe4a72022-12-22T03:46:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-10-01710.3389/fimmu.2016.00411211464NFAT2 regulates generation of innate-like CD8+ T lymphocytes and CD8+ T lymphocytes responsesEmilia Pachulec0Vanessa Neitzke-Montinelli1Joao P.B. Viola2Instituto Nacional de Cancer (INCA)Instituto Nacional de Cancer (INCA)Instituto Nacional de Cancer (INCA)NFAT2 null mutant mice die in utero of 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 lymphocytes responses. We report that NFAT2 is phosphorylated and inactive in the cytoplasm of naive CD8+ T cells, and upon TCR stimulation 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 nonconventional innate-like CD8+ T cells. These cells were CD122+, rapid producer of IFN-γ and had characteristics of conventional memory CD8+ T cells. We also observed an expansion of PLZF+ expressing CD3+ thymocytes 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 influence significantly differentiation of CD8+ T cells into cytotoxic effector cells, but reduced theirs IFN-γ production. This work documents NFAT2 as a negative regulator of innate-like CD8+ T cells development. NFAT2 is required for a complete CD8+ T cells responses at suboptimal TCR stimulation and regulates IFN-γ production by cytotoxic CD8+ T cells in vitro.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00411/fullPLZFIFN-γNFAT2CD8+ T lymphocytesinnate-like CD8+ T cells |
| spellingShingle | Emilia Pachulec Vanessa Neitzke-Montinelli Joao P.B. Viola NFAT2 regulates generation of innate-like CD8+ T lymphocytes and CD8+ T lymphocytes responses Frontiers in Immunology PLZF IFN-γ NFAT2 CD8+ T lymphocytes innate-like CD8+ T cells |
| title | NFAT2 regulates generation of innate-like CD8+ T lymphocytes and CD8+ T lymphocytes responses |
| title_full | NFAT2 regulates generation of innate-like CD8+ T lymphocytes and CD8+ T lymphocytes responses |
| title_fullStr | NFAT2 regulates generation of innate-like CD8+ T lymphocytes and CD8+ T lymphocytes responses |
| title_full_unstemmed | NFAT2 regulates generation of innate-like CD8+ T lymphocytes and CD8+ T lymphocytes responses |
| title_short | NFAT2 regulates generation of innate-like CD8+ T lymphocytes and CD8+ T lymphocytes responses |
| title_sort | nfat2 regulates generation of innate like cd8 t lymphocytes and cd8 t lymphocytes responses |
| topic | PLZF IFN-γ NFAT2 CD8+ T lymphocytes innate-like CD8+ T cells |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00411/full |
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