Mitogenic response of human thymocytes: identification of functional Ca2+-dependent and independent signals.
In contrast to peripheral blood mononuclear cells (PBMC), human thymocytes do not exhibit a proliferative response to the T cell mitogens phytohaemagglutinin (PHA), concanavalin A (Con A), or Staphylococcal protein A (SPA). In thymocytes and PBMC, Con A and PHA induce increases in free cytosolic calcium concentrations [( Ca2+]i). Since both Con A and PHA induce similar increases in [Ca2+]i in thymocytes and PBMC, the absence of thymocyte proliferation was not due to an inability to induce an increase in [Ca2+]i. The lack of proliferative response was secondary to the failure of the mitogens to induce interleukin 2 (IL-2) production. Incubation of mitogen-treated thymocytes with phorbol esters reconstituted IL-2 production and the proliferative response indicating that the cells were indeed activated by the mitogens. Similarly, addition of exogenous recombinant IL-2 also induced mitogen-treated thymocytes to proliferate. This IL-2-dependent proliferation established that SPA, Con A, and PHA triggered the expression of biologically active IL-2 receptors. Since an increase in [Ca2+]i is a prerequisite, and possibly a trigger, for IL-2 production, the failure of PHA, Con A, or SPA to result in thymocyte proliferation may be due to an inability of thymocytes to respond to increases in [Ca2+]i with subsequent IL-2 production.
D002118:Calcium / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology*
D007375:Interleukin-1; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D013936:Thymidine