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TNFRI is a positive T‐cell costimulatory molecule important for the timing of cytokine responses
Author(s) -
Evangelidou Maria,
Tseveleki Vivian,
Vamvakas SotirisSpyros,
Probert Lesley
Publication year - 2010
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2010.12
Subject(s) - tumor necrosis factor alpha , t cell receptor , t cell , cytokine , il 2 receptor , chemistry , biology , microbiology and biotechnology , immunology , immune system
Tumor necrosis factor (TNF)‐ and TNF receptor I (TNFRI)‐deficient mice are resistant to initiation and show delayed resolution of disease in paradigms of autoimmune disease, but the contribution of TNF/TNFRI signaling to T‐cell activation and effector responses has not been determined. In this study, we investigated the role of TNFRI in T‐cell receptor (TCR)‐mediated T‐cell activation in vitro and in vivo using CD3 + ‐enriched primary T cells and mice deficient in TNFRI. Following TCR engagement, TNFRI knockout (KO) T cells showed significantly delayed proliferation, cell division, upregulation of interleukin 2 (IL‐2) and IL‐2 receptor α chain (CD25) mRNA and cell‐surface expression of CD25 compared with wild‐type (WT) cells. Thus, WT and TNFRI KO cells showed equivalent proliferation peaks at 48 and 72 h, respectively. TNFRI KO mice also developed a defective primary T‐cell response to ovalbumin and an acute contact hypersensitivity response to oxazolone (4‐ethoxymethylene‐2‐phenyl‐2‐oxazolin‐5‐one). However, TNFRI KO splenocytes that were stimulated by TCR engagement in vitro for 96 h produced significantly higher intracellular levels of interferon‐γ (IFN‐γ), IL‐2 and TNF‐α, but not IL‐17, compared with WT cells, in correlation with their relatively higher proliferation rate at this time point. Further, TCR‐stimulated CD3 + ‐enriched TNFRI KO T cells showed similarly higher production and secretion of IFN‐γ and IL‐2 compared with WT, suggesting that TNFRI‐mediated cytokine regulation might involve a T‐cell autonomous effect. Our results show a novel role for TNFRI as a positive T‐cell costimulatory molecule that is important for timely T‐cell activation and effector cytokine production and the development of primary immune responses in mice.