Modulation of High-Affinity Interleukin 2 Receptors on Activated Human T Lymphocytes by Activators of Protein Kinase C

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Abstract
Phorbol myristate acetate (PMA) and 1-oleoyl-2-acetyl-rac-glycerol (OAG) are shown to induce a rapid (within 30 min) down-regulation of the capacity of activated human T lymphocytes to bind interleukin 2. This was associated with a manifold increases in membrane-associated protein kinase C, whereas no change in free cytoplasmic calcium was observed. In contrast, a 10-fold increase in free cytoplasmic calcium by inomycin had no effect on interleukin 2 binding or subcellular distribution of protein kinase C. The reduction of interleukin 2 binding was caused by a decreased number of high-affinity interleukin 2 receptors, whereas the affinity of the remaining receptors was unchanged. However, PMA and OAG had no effect on the rate of internalization of the interleukin receptor. These data suggest that activation of protein kinase C, but not an increase in free cytoplasmic calcium, leads to a rapid decrease in the number of high-affinity interleukin 2 receptors on activated human T lymphocytes. However, the mechanism and biological importance of the phenomenon have to be further elucidated.