Phorbol myristate acetate and calcium ionophore A23187-stimulated human T cells do not express high-affinity IL-2 receptors.
Phorbol myristate acetage (PMA) and Ca2+ ionophore A23187 mimic early signal transduction pathways and activate purified human T cells to secrete large quantities of interleukin-2 (IL-2) and to proliferate. Despite producing 50-100-fold more IL-2 than phytohaemagglutinin (PHA)-activated peripheral blood lymphocytes (PBL), PMA/A23187-stimulated human T cells proliferate less than cells activated by PHA. Washing the cells to remove PMA/A23187 was found to increase cellular proliferation two to five-fold. High-affinity IL-2R (HA-IL-2R) were found to be expressed by human T cells that had been washed 24 hr after PMA/A23187 stimulation and recultured without stimulus for an additional 48 hr, but not by T cells constantly exposed to PMA/A23187 for 72 hr. Radioligand binding studies with [125I]IL-2 demonstrated that while the alpha (p55) and beta (p70-75) subunits of HA-IL-2R were both present on the constant PMA/A23187-stimulated T cells, they did not appear to associate to form functional HA-IL-2R. This defect in the expression of bio-active HA-IL-2R on constant PMA/A23187-stimulated human T cells seems to account for their low proliferative response.
Chopra
R K
RK
Clinical Immunology Section, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Powers
D C
DC
Adler
W H
WH
Nagel
J E
JE
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001681:Biological Assay; D000001:Calcimycin / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D007476:Ionophores; D015375:Receptors, Interleukin-2; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate