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 particularly 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.
Górski
A
A
Department of Immunology, Warsaw Medical School, Poland.
Grieb
P
P
Korczak-Kowalska
G
G
Wierzbicki
P
P
Stepień-Sopniewska
B
B
Mrowiec
T
T
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D017338:Cladribine / Q000494:pharmacology*; D016650:Fluorescein-5-isothiocyanate; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D006681:HLA-D Antigens; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D017338:Cladribine; D016650:Fluorescein-5-isothiocyanate