Induction of high-affinity interleukin 2 receptors on human T lymphocytes. The role of calcium and protein kinase C.

The relationship between free cytoplasmic calcium, activation of protein kinase C (PKC) and expression of high-affinity interleukin 2 receptors (HA-IL-2R) on human T lymphocytes was studied. Induction of HA-IL-2R by phytohaemagglutinin (PHA) was associated with an increase in free cytoplasmic calcium and a transient increase in membrane-associated PKC. However, whereas addition of EGTA inhibited induction of receptors by PHA, addition of the PKC-inhibitor H7 did not. 12-o-tetradecanoyl-phorbol-13-acetate (PMA) and 1-oleoyl-2-acetyl-rac-glycerol (OAG) were both found to activate and translocate PKC. However, only PMA induced expression of HA-IL-2R. Not surprisingly, the effect of PMA was independent of extracellular calcium, but was inhibited by H7. Furthermore, a correlation between the number of HA-IL-2R and free cytoplasmic calcium upon stimulation with ionomycin was observed. Associated with the rise in intracellular calcium, the ionophore caused a slight increase in membrane-associated PKC. Also, addition of H7 inhibited expression of HA-IL-2R. Finally, OAG and ionomycin acted synergistically on expression of HA-IL-2R. In conclusion, induction of HA-IL-2R requires at least two different signals and neither activation of PKC nor an increase in free cytoplasmic calcium is sufficient. However, these two signals may act synergistically. There is evidence for both a PKC- and calcium-independent pathway.