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Published online before print July 1, 2003

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(Journal of Leukocyte Biology. 2003;74:572-582.)
© 2003 by Society for Leukocyte Biology

Regulation of TCR-mediated T cell activation by TNF-RII

Immunology Outpatient Clinic, Vienna, Austria

¹Correspondence: Immunology Outpatient Clinic, Schwarzspanierstraße 15/1, A-1090 Vienna, Austria. E-mail: hermann.wolf{at}itk.at

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- 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- and TNF-. 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.

Key Words: T cell receptor • TNF- • IL-2 • Ca⁺⁺ flux

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