Weak TCR stimulation induces a calcium signal that triggers IL-4 synthesis, stronger TCR stimulation induces MAP kinases that control IFN-γ production

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Abstract
Th1 and Th2 cells produce different cytokines and have distinct functions. Th1/Th2 cell differentiation is influenced, among other factors, by the nature of TCR‐MHC interactions. However, how the TCR transduces a signal resulting in IFN‐γ or IL‐4 production is a matter of debate. For example, some authors reported a loss of calcium signaling pathway in Th2 cells. We used a T cell hybridoma producing IL‐4 upon weak TCR stimulation and both IL‐4 and IFN‐γ for strong TCR engagement as a model to study how TCR signaling pathways are differentially activated in both conditions of stimulation and how this influences the production of cytokines. We show that: (1) the calcium response is identical following weak and strong TCR stimulation; (2) mitogen‐activated protein kinase(MAPK) activation is a gradual phenomenon depending upon the strength of TCR activation; (3) a calcium response, even weak, triggers IL‐4 expression; (4) IFN‐γ synthesis requires not only a calcium response but also MAPK activation. The MAPK pathway is dispensable for IL‐4 production, although it amplifies IL‐4 synthesis upon strong TCR stimulation; (5) TCR‐induced IL‐4 production also dependson calcium signaling in Th2 cells, while IFN‐γ synthesis is dependent, in addition, on MAPK activation in Th1 cells.

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