Multiphasic modulation of signal transduction into T lymphocytes by monoiodoacetic acid as a sulfhydryl reagent.
Actions of monoiodoacetic acid (MIA) as a sulfhydryl reagent on the different stages of the T cell receptor (TCR)-mediated signal transduction were examined. MIA (1 mM) prevented anti-TCR (CD3) monoclonal antibody (mAb)-induced energy-dependent receptor capping but at the same time promoted the anti-CD3 mAb/mitogen-induced tyrosine phosphorylation of the T cell activation-linked cellular proteins of 120, 80, 70, 56, and 40 kDa. Relatively low concentration (0.01 mM) of MIA further promoted anti-CD3 mAb-induced transcription of c-fos, production of IL-2, and cell surface expression of IL-2 receptors. The MIA-promoted TCR-mediated IL-2 production actually required signal transduction that could be inhibited by cyclosporin A, genistein, or H-7. In contrast, the same concentration of MIA as promoted the signal transduction for cell activation severely inhibited the anti-CD3 mAb-triggered signal delivery for cell proliferation, selectively at its early stage. We conclude from these results that MIA differentially affects various steps of signaling into T lymphocytes, suggesting that there exist multiple sites of MIA-sensitive or redox-linked control in the signal cascade.
Department of Immunology, Nagoya University School of Medicine, Japan.
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Yi
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Akhand
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Ohata
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Ohkusu
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Kato
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Iwamoto
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Isobe
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Hamaguchi
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017781:Genes, Immediate-Early; D007376:Interleukin-2 / Q000096:biosynthesis; D007461:Iodoacetates / Q000494:pharmacology*; D019807:Iodoacetic Acid; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
D017252:CD3 Complex; D007376:Interleukin-2; D007461:Iodoacetates; D015375:Receptors, Interleukin-2; D013439:Sulfhydryl Reagents; D014443:Tyrosine; D019807:Iodoacetic Acid