Activation of IL 1-dependent and IL 1-independent T cell lines by calcium ionophore and phorbol ester.
We have studied the activation of interleukin 1 (IL 1)-dependent and IL 1-independent T cell lines, specifically their capacity to produce and secrete interleukin 2 (IL 2). The IL 1-dependent T cell lymphoma LBRM33-1A5.47, which requires phytohemagglutinin (PHA) and IL 1 to produce IL 2, was compared with the IL 1-independent T cell lymphoma LBRM33-5A4 and T cell hybridomas DO-11.10/S4.4 and 3DO-54.8. The latter hybridomas do not require exogenous IL 1 to produce IL 2 in response to mitogens or ovalbumin (OVA)/I-Ad. Even though IL 1 is not required by these IL 1-independent T cell lines, we tested whether IL 1 could modulate their response but found no significant effect of exogenous IL 1. We then studied the activation of these T cell lines by the calcium ionophore A23187 and phorbol myristate acetate (PMA). In the case of the IL 1-dependent line LBRM33-1A5.47, there was a strong response when both A23187 and PMA were used simultaneously. We subsequently found that A23187 can replace PHA, and PMA can replace IL 1 in the activation of this cell line to IL 2 production. These observations suggest that the signal(s) provided by PHA and IL 1 involve at least in part a calcium flux, and activation of protein kinase C. Parallel experiments with the use of the IL 1-independent T cell lines showed a strong response to both agents when used simultaneously. A modest response observed to A23187 alone was always enhanced by the addition of PMA. No response was observed to PMA alone. IL 1-rich P388D1 supernatant could replace the enhancing effect of PMA in the response of the IL 1-independent T cell lines. We suggest that the activating signals provided by A23187 and PMA are at least part of the sequence of events that lead to production of IL 2 in either IL 1-dependent or IL 1-independent T cell lines. In IL 1-independent T cell lines, however, both of the activating signals studied may be delivered through stimulation of the Antigen-MHC T cell receptor.
Zlotnik
A
A
Daine
B
B
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007941:Leukemia P388 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008223:Lymphoma / Q000276:immunology; D051379:Mice; D010704:Phorbols / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007375:Interleukin-1; D007376:Interleukin-2; D010704:Phorbols; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate