Molecular basis of type2 helper T cell differentiation reading to lgE production

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The central role of Type-2 helper T (Th2) cells in the development of allergic responses and immune responses against helminthic parasites is well documented. The differentiation of Th2 cells from naive T cells requires both the recognition of antigen by T-cell antigen receptors (TCR) and the activation of downstream signal transduction molecules of the IL-4 receptor (IL-4R) pathway, including Jak1, Jak3, and STAT6. Little is known, however, about how these two distinct pathways cooperate with each other to induce Th2 cells. Here we use a T cell specific H-ras-dominant negative transgenic mouse to show that TCR-mediated activation of Ras/Mitogen-activated protein kinase (MAPK) pathway alters IL-4R function and is required for Th2 cell differentiation. The enhancement of IL-4R signaling appears to be a consequence of both direct crosstalk with the TCR signaling pathway and increased protein expression of downstream signaling molecules of the IL-4R pathway. Therefore, successful Th2 differentoation depends on the effectiveness of the TCR-mediated activation of the Ras/MAPK pathways in modifying the IL-4R-mediated signaling pathway. In another words, we present evidence that the TCR-mediated Ras/MAPK activation controls IL4R-mediated signaling and determines the direction of helper T cell differentiation. Thus, our data suggest that the lineage choices made by naive Th cells following antigen, stimulation are clearly influenced by.