Effect of immunosuppressive agents on human T and B lymphoblasts.
We have studied the effects of various immunosuppressive drugs on the growth of human-derived T (MOLT-4) and B (MGL-8) lymphoblasts. In addition, we have examined whether the lymphotoxic effect of any of these drugs could be attributed to inhibition of either adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP). Results indicated that 1-beta-D-arabinofuranosylcytosine (Ara-C), methotrexate and chlorambucil were four to seven times more toxic for T than for B cells, while azathioprine, 6-thioguanine, 6-mercaptopurine, and 5-fluorouracil were highly toxic for both T and B cells. Cyclophosphamide and oxisuran were lymphotoxic only at concentrations exceeding 300 microM. Deoxyadenosine (50 microM), deoxyguanosine (10 microM) and deoxycoformycin (10 microM) failed to enhance T cell toxicity when individually combined with each drug. None of the drugs tested inhibited T or B lymphoblast ADA or PNP activity. With the exception of Ara-C, neither dATP nor dGTP accumulated in T lymphoblasts incubated in the presence of any of the drugs. We conclude that the cell culture system used in this investigation is useful for identifying lymphotoxic and T cell-specific immunosuppressive agents. However, none of the drugs studied appeared to function as an inhibitor of, or a competitive substrate for, either ADA or PNP.
D058892:Adenosine Deaminase Inhibitors; D001402:B-Lymphocytes / Q000187:drug effects*; D002478:Cells, Cultured; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000187:drug effects*
D058892:Adenosine Deaminase Inhibitors; D003838:Deoxyadenine Nucleotides; D003848:Deoxyguanine Nucleotides; D007166:Immunosuppressive Agents; C029603:deoxyguanosine triphosphate; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D009700:Nucleoside Deaminases; C026600:2'-deoxyadenosine triphosphate