Calcium Ionophore A23187 Induces Interleukin 2 Reactivity in Human T Cells

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.