Calcium Ionophore A23187 Induces Interleukin 2 Reactivity in Human T Cells

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Abstract
In the present study the activation of purified human T lymphocytes by the calcium ionophore A23187 was analysed in the light of current concepts of receptor-linked inositol lipid metabolism. It was found that A23187 was only slightly mitogenic, with a narrow optimum at 400-500 nM. The proliferation could be blocked by anti-Tac ascites at 10-3 dilution, suggesting an interleukin 2 (IL-2)-dependent pathway of activation. However, an unexpectedly large proportion of A23187-stimulated cells expressed the IL-2 receptor. Reculturing the cells with exogenous IL-2 after removal of A23187 resulted in strongly enhanced proliferation. Phorbol myristic acetate (PMA) at non-mitogenic concentrations exerted an extremely strong synergistic effect on A23187-induced cell proliferation, which was, again, mediated via an IL-2-dependent pathway. Supernatants of A23187-stimulated T cells did not contain detectable amounts of IL-2. Combination of PMA and A23187 resulted in considerable IL-2 production. It is concluded that A23187 induces the expression of IL-2 receptors without concurrent stimulation of IL-2 production, thus allowing only low levels of proliferation. Addition of exogenous IL-2 or of PMA restores the imbalance between the occurrence of IL-2 and its receptor and results in high rates of proliferation.