The Journal of Immunology, Vol 151, Issue 11 6051-6061, Copyright © 1993 by American Association of Immunologists

ARTICLES

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

T Tamura, T Yanagida and H Nariuchi
Department of Allergology, University of Tokyo, Japan.

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.

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