Regulation of TCR-mediated T cell activation by TNF-RII.
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-alpha 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-gamma and TNF-alpha. 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.
Aspalter
Rosa Maria
RM
Immunology Outpatient Clinic, Vienna, Austria.
Eibl
Martha Marianne
MM
Wolf
Hermann Maximilian
HM
D015703:Antigens, CD / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D018106:CD28 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10