Difference in signal transduction pathway for IL-2 and IL-4 production in T helper 1 and T helper 2 cell clones in response to anti-CD3.
To elucidate Th2 cell clone activation mechanism through TCR-CD3 complex, we examined the reactivity of Th2 cell clones to soluble anti-CD3 in the absence of accessory cells or costimulator. The soluble anti-CD3 stimulated IL-4 production of Th2 cell clones as efficiently as specific Ag. IL-4 production of Th2 cell clones was consistent with the elevation of intracellular free Ca2+ concentration ([Ca2+]i). The elevation was slow and sustained but occurred consistently after the anti-CD3 stimulation in all Th2 cell clones tested. The [Ca2+]i elevation appeared to depend on Ca2+ influx because it could not be observed in Ca(2+)-free medium. Several chemicals such as cholera toxin, neomycin, and herbimycin A, which have been shown to block phosphatidylinositol-4,5-bisphosphate (PIP2) breakdown pathway or protein tyrosine kinase activation, exerted no effect on the IL-4 production. In accordance with these findings, neither PIP2 breakdown nor protein tyrosine phosphorylation was observed in Th2 cell clones stimulated with anti-CD3. The inclusion of anti-CD4 in culture and the depletion of protein kinase C (PKC) did not affect IL-4 production of Th2 cell clones either. These findings support a hypothesis that Th2 cell clones use a signaling pathway for IL-4 production that is independent of protein tyrosine kinase, PIP2 breakdown or PKC, and that the [Ca2+]i elevation is the only pathway common to an IL-2 production of Th1 cell subset.
Tamura
T
T
Department of Allergology, University of Tokyo, Japan.
Yanagida
T
T
Nariuchi
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016227:Benzoquinones; D017252:CD3 Complex / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D002999:Clone Cells; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D047029:Lactams, Macrocyclic; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009355:Neomycin / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016227:Benzoquinones; D017252:CD3 Complex; D007376:Interleukin-2; D047029:Lactams, Macrocyclic; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D011809:Quinones; D017828:Rifabutin; D015847:Interleukin-4; C020754:herbimycin; D002772:Cholera Toxin; D011493:Protein Kinase C; D009355:Neomycin; D002118:Calcium