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Regulation of TCR‐mediated T cell activation by TNF‐RII
Author(s) -
Aspalter Rosa Maria,
Eibl Martha Marianne,
Wolf Hermann Maximilian
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0303112
Subject(s) - t cell receptor , biology , cd28 , tumor necrosis factor alpha , t cell , microbiology and biotechnology , cytokine , il 2 receptor , immunology , immune system
In the present study, we investigated the role of tumor necrosis factor receptor II (TNF‐RII) in human T cell activation induced via the T cell receptor (TCR) in an antigen‐presenting cell‐independent system. Our results confirm that interaction of TNF‐α with TNF‐RII but not TNF‐RI is directly costimulatory to TCR‐mediated T cell activation, thereby augmenting T cell proliferation, expression of T cell activation markers (CD25, human leukocyte antigen‐DR, TNF‐RII), and secretion of cytokines such as interferon‐γ and TNF‐α. In contrast to the well‐defined costimulatory molecule CD28, costimulation via TNF‐RII showed significant differences in kinetics, requirement for cross‐linking, redundancy of intracellular signaling pathways involved, and the capacity to induce interleukin (IL)‐2, IL‐10, and IL‐13 secretion. In addition, cross‐linking TNF‐RII had the capacity to down‐regulate TCR/CD28‐induced Ca ++ mobilization, IL‐2 mRNA expression, and IL‐2 and IL‐10 secretion. Taken together, our findings demonstrate that TNF‐RII plays a unique role among the T cell costimulatory molecules, as TNF‐RII ligation can have positive and negative effects on TCR‐dependent signaling. TNF‐RII cross‐linking has an inhibitory effect on early TCR signaling events proximal to induction of Ca ++ flux, which ultimately leads to modulation of the T cell cytokine pattern expressed.