Effect of Immunosuppressive Agents on Human T and B Lymphoblasts

Biochem Pharmacol. 1983 Mar 1;32(5):805-10. doi: 10.1016/0006-2952(83)90580-4.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Deaminase Inhibitors*
  • B-Lymphocytes / drug effects*
  • Cells, Cultured
  • Deoxyadenine Nucleotides / metabolism
  • Deoxyguanine Nucleotides / metabolism
  • Humans
  • Immunosuppressive Agents / toxicity*
  • Nucleoside Deaminases / antagonists & inhibitors*
  • Pentosyltransferases / antagonists & inhibitors*
  • Purine-Nucleoside Phosphorylase / antagonists & inhibitors*
  • T-Lymphocytes / drug effects*

Substances

  • Adenosine Deaminase Inhibitors
  • Deoxyadenine Nucleotides
  • Deoxyguanine Nucleotides
  • Immunosuppressive Agents
  • deoxyguanosine triphosphate
  • Pentosyltransferases
  • Purine-Nucleoside Phosphorylase
  • Nucleoside Deaminases
  • 2'-deoxyadenosine triphosphate