Evidence for an interleukin-independent pathway for human lymphocyte activation.

Abstract

Though lectin mitogen stimulation of T cell proliferation is an interleukin 1 (IL 1), interleukin 2 (IL 2) dependent process, the calcium ionophore A23187 [calcimycin] 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 the inability of exogenous IL 2 to augment A23187-induced proliferation, and the inability of the monoclonal antibody anti-Tac (with specificity for the human IL 2 receptor) to inhibit proliferation mediated by A23187. In cultures stimulated with the lectin mitogen phytohemagglutinin, additional IL2 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 the results could not be explained by excessive amounts of endogenous IL 2 interfering with the blocking action of the antibody. The action of A23187 as a human lymphocyte mitogen may be the result of at least 2 pathways, one dependent on the interleukin, cell interactions and the other independent of these mediators.