Interleukin 1-mediated activation of interleukin 4 (IL 4)-producing T lymphocytes. Proliferation by IL 4-dependent and IL 4-independent mechanisms.
The role of IL 1 in the activation of IL 4-producing murine T cell clones was investigated by using a calcium ionophore (ionomycin) or a phorbol ester (12-O-tetradecanoylphorbol 13-acetate; TPA) as T cell receptor-independent costimuli. The use of these pharmacologic agents to investigate IL 1-mediated T cell activation revealed two distinct mechanisms of activation. IL 1 in combination with ionomycin (iono/rIL 1) stimulated a proliferative response that was associated with the production of IL 4 as measured by lymphokine bioassay and mRNA studies. Furthermore, inhibition of this proliferative response with an anti-IL 4 monoclonal antibody or cyclosporine indicated that IL 4 functions as an autocrine growth factor. In contrast, IL 1 synergized with TPA (TPA/rIL 1) to induce proliferation in the absence of either IL 4 or IL 2 gene transcription or lymphokine secretion. The IL 4-independence of this activation mechanism was further supported by the failure of both anti-IL 4 antibodies and cyclosporine to inhibit the response. In addition, activation by TPA/rIL 1 caused no detectable alteration in cytoplasmic calcium levels. Both IL 4-dependent and IL 4-independent activation responses were associated with the expression of functional receptors for IL 2 as well as IL 4. Characterization of these activation responses suggests that the synergistic activity of IL 1 during T cell activation is multipotential. The nature of an IL 1-dependent T cell growth response, therefore, may vary depending on the balance of intracellular signals generated concurrently through the T cell receptor complex and other regulatory surface molecules.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology; D004357:Drug Synergism; D004987:Ethers / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015847:Interleukin-4; D015759:Ionomycin; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D004987:Ethers; D006133:Growth Substances; D007375:Interleukin-1; D008222:Lymphokines; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate