CLADRIBINE (2-CHLORO-DEOXYADENOSINE, CDA) - AN INHIBITOR OF HUMAN B AND T-CELL ACTIVATION IN-VITRO

We have previously shown that the novel immunosuppressive agent cladribine (CDA) inhibits human T and B cell lymphoproliferative responses and immunoglobulin synthesis in vitro, yet appears to be particulary efficacious as an inhibitor of B cell responses. We now report the effects of CDA on the human mixed lymphocyte reaction and on expression of T and B cell activation markers. CDA produced a significant inhibition of lymphocyte proliferation in human mixed lymphocyte reactions at a concentration of 10 nM. At concentrations of 10-100 nM the drug inhibited phytohaemagglutinin-induced expression of CD25 and HLA-D (by approximately 50%), but not phorbol myristate acetate-induced expression of CD69 on purified human T cells. At a concentration of 10 nM CDA totally abolished Staphylococcus aureus Cowan-induced expression of CD25 on purified B cells. These findings confirm that CDA is a potent immunosuppressive agent with some selectivity towards B cells. The drug may have potentially wide applications in clinical immunosuppression.