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 cladri bine (CDA) inhibits human T and B cell lymphoproliferative responses a nd immunoglobulin synthesis in vitro, yet appears to be particulary ef ficacious as an inhibitor of B cell responses. We now report the effec ts 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 inhibi ted phytohaemagglutinin-induced expression of CD25 and HLA-D (by appro ximately 50%), but not phorbol myristate acetate-induced expression of CD69 on purified human T cells. At a concentration of 10 nM CDA total ly abolished Staphylococcus aureus Cowan-induced expression of CD25 on purified B cells. These findings confirm that CDA is a potent immunos uppressive agent with some selectivity towards B cells. The drug may h ave potentially wide applications in clinical immunosuppression.