Does interleukin 2 stimulus-response coupling result in generation of intracellular second messengers?
The binding of interleukin 2 (IL 2) to specific cell surface receptors provides a unique proliferative stimulus to sensitive T-lymphocytes. The purpose of this investigation was to examine the hypothesis that IL 2 stimulus-response coupling in the IL 2-dependent murine T-lymphocyte clone CTLL-2 employed some of the intracellular second messengers used by other growth factors. No evidence was obtained to implicate changes in intracellular Ca2+ concentrations, protein kinase C activation, or stimulation of the Na+/H+ antiporter or the Na+/K+ ATPase as requirements for stimulation by recombinant human IL 2. Pertussis toxin did not inhibit IL 2-driven growth of CTLL-2, and while cholera toxin did inhibit growth, its effect was optimal 6 to 8 hr after addition of IL 2 and could be mimicked by increased intracellular cyclic-AMP. Thus, guanine nucleotide-binding regulatory proteins do not appear to be involved in stimulation by this lymphokine. Together, these data suggest that IL 2 may not use any of the same types of intracellular second messengers generated subsequent to the binding of antigen or mitogen by T-lymphocytes.
LeGrue
S J
SJ
Department of Immunology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030.
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007376:Interleukin-2; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium