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

Journal of Leukocyte Biology

Hermann Maximilian Wolf¹  Martha Marianne Eibl¹  Rosa Maria Aspalter¹ 

[1] Immunology Outpatient Clinic, Vienna, AustriaImmunology Outpatient Clinic, Vienna, AustriaImmunology Outpatient Clinic, Vienna, Austria

关键词: T cell receptor;    TNF-α;    IL-2;    Ca⁺⁺ flux;   

DOI  :  10.1189/jlb.0303112

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown