Autologous mixed-lymphocyte reaction in man. XVII. In vitro effect of ion channel-blocking agents on the autologous mixed-lymphocyte response.
The in vitro effect of ion channel-blocking agents verapamil (V), 4-aminopyridine (4AP), tetraethylammonium (TEA), and quinine (Q) was examined on the proliferative response of human peripheral blood T lymphocytes in the autologous mixed-lymphocyte reaction (AMLR). All the above channel blockers in a dose-dependent manner inhibited the AMLR. Tetramethylammonium (TMA), an analog of TEA that does not block K+ channel currents, did not inhibit the AMLR. 4AP at 1 mM/ml concentration inhibited the expression of IL-2 receptors, as defined by monoclonal antibody anti-Tac, on T-cell activated in the AMLR. In vitro addition of recombinant interleukin 2(rIL-2) completely corrected the inhibition of the AMLR by channel blockers. Furthermore, the concentrations of ion channel blockers required for blocking 50% response of T cells in the AMLR was much lower than that reported for 50% block of T-cell proliferation in response to phytohemagglutinin or in allogeneic mixed-lymphocyte culture (MLC). These data suggest a role of ion channels in T-cell functions and show that the AMLR provides a more sensitive system, as compared to lectin stimulation or MLC, to examine any immunosuppressive effects of ion channel-blocking agents in disease states where they are used as therapeutic modalities.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000631:Aminopyridines; D007376:Interleukin-2; D007473:Ion Channels; D000644:Quaternary Ammonium Compounds; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D011803:Quinine; D015761:4-Aminopyridine; D014700:Verapamil; C027917:tetramethylammonium