Evidence for an interleukin-independent pathway for human lymphocyte activation.
Though lectin mitogen stimulation of T-cell proliferation is an interleukin 1- (IL 1), interleukin 2- (IL 2) dependent process, the calcium ionophore A23187 may be able to initiate T-lymphocyte proliferation by an additional pathway. That the action of A23187 is IL 1 independent was demonstrated by its ability to stimulate monocyte-depleted cells without the addition of exogenous IL 1. The IL 2 independence of A23187 was indicated by (i) the inability of exogenous IL 2 to augment A23187-induced proliferation and (ii) the inability of the monoclonal antibody anti-Tac (with specificity for the human IL 2 receptor) to inhibit proliferation mediated by A23187. By contrast, in cultures stimulated with the lectin mitogen phytohemagglutinin, additional IL 2 considerably increased proliferation, whereas anti-Tac routinely caused 60-90% inhibition. Although the ionophore caused some IL 2 production and resulted in IL 2 receptor expression, quantitative studies showed that our results could not be explained by excessive amounts of endogenous IL 2 interfering with the blocking action of the antibody. Therefore, these data suggest that the action of A23187 as a human lymphocyte mitogen may be the result of at least two pathways--one dependent on the interleukin-cell interactions and the other independent of these mediators.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000900:Anti-Bacterial Agents; D007375:Interleukin-1; D007376:Interleukin-2; D000001:Calcimycin