The expression and the regulatory role of OX40 and 4-1BB heterodimer in activated human T cells.

OX40 and 4-1BB are members of the tumor necrosis factor (TNF) family of costimulatory receptors whose signaling is important for differential immune responses mediated by CD4+ or CD8+ T cells. Although activated T cells may acquire OX40/4-1BB double-positive phenotype and signaling from each receptor is expected to influence cell functions, ...
the relevance between OX40 and 4-1BB has never been investigated before. While we were investigating the expression of OX40 and 4-1BB on activated human T cells, we found that they colocalize. The study of receptor gene-transfected cells showed that both receptors coendocytose and the complex of OX40 and 4-1BB was detected by specific ligands or antibodies (Abs). The heterodimer of OX40 and 4-1BB was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreduced conditions and was associated with the tumor receptor-associated factor (TRAF) family proteins in a unique manner. Furthermore, the stimulation of OX40/4-1BB rendered cells sensitive to apoptosis induced by TNF-alpha that accompanied reduced activation of nuclear factor-kappaB (NF-kappaB). Finally, the OX40/4-1BB stimulation repressed the mitogen response in activated CD25+CD4+ T cells and preactivated CD8+ T cells. Thus, the OX40/4-1BB heterodimer appears to represent a unique regulatory receptor in activated T cells.
Mesh Terms:
Antigens, CD, Antigens, CD137, Apoptosis, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cells, Cultured, Dimerization, Endocytosis, Humans, Lymphocyte Activation, NF-kappa B, Protein Binding, Receptors, Nerve Growth Factor, Receptors, OX40, Receptors, Tumor Necrosis Factor, T-Lymphocytes, Transfection, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, Tumor Necrosis Factor-alpha
Blood
Date: Sep. 15, 2005
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