Abstract
CD134 (OX40) is a new member of the tumor necrosis factor receptor (TNFR) superfamily. The influence of CD134 on perforin-mediated cytolysis remains obscure. In this study, human peripheral blood mononuclear cells (PBMC) were induced with phytohemagglutinin (50 µg/mL), by using anti-CD134 blocking monoclonal antibody (MAb; 1, 5, and 10 µg/mL) for 6, 12, 24, and 48 h. Perforin-mediated cytolysis against human erythrocytes of PBMC was detected. The expression of perforin mRNA and protein was also measured by reverse transcription–polymerase chain reaction and flow cytometry. Our data showed that the perforin-mediated cytolysis of PBMC was downregulated by various concentrations of anti-CD134 blocking MAb for different times and reached a minimum at 24 h at any concentration. Anti-CD134 blocking MAb induced downregulation of perforin-mediated cytolysis of PBMC in a dose-dependent manner in the range of 1–5 µg/mL. Perforin- mediated cytolysis of PBMC reached a plateau when the concentration of anti-CD134 blocking MAb exceeded 5 µg/mL. Anti-CD134 blocking MAb also induced the inhibition of the expression of perforin protein and mRNA in PBMC. In conclusion, anti-CD134 blocking MAb inhibits perforin-mediated cytolysis of PBMC by, at least in some part, decreasing the production of preforin, which may be useful in treating several autoimmune diseases.
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