Search for transcriptional factor which regulates helper T cell Th1/Th2 balance.

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Lewis rats are prone to T helper (Th)1 immune responses, whereas Brown Norway (BN) rats are susceptible to Th2 immune responses. Yet, the precise mechanism of induction of the different outcome between these two strains remained elusive. We investigated the expression levels of some cytokines, their receptors and accessory molecules, responsible for the polarization of antigen-specific immune response into a predominant Th1 or Th2 profile in Lewis and BN rats. We observed clear differences between these strains in the expression of IL-12p40, which was high in lymph node cells of Lewis rats. Upregulation of the expression of IL-12 receptor β1, β2, IFN-γ receptor α and β genes were more prominent in Lewis rats rather than BN rats. Thus, IL-12 production by macrophages or dendritic cells seems to be essential event for the activation of Th1 cellsTo understand the mechanism of Th1 activaion in Lewis rats, we investigates process of antigen-presentation. Human monocytic leukemia THP-1 cells differentiate into macrophage-like cells when treated with 12-O-tetradecanoyl phorbol-13-acetate (TPA). During this process. IFN-γ-inducible expression of HLA-DRα is markedly enhanced. The enhancement of HLA-DRα expression is at least due to the TPA-dependent induction of the IFN-γ receptor genes. We have studied the mechanism of TPA-induced up-regulation of the IFN-γ R1 gene and identified TPA-responsive element in the promoter of IFN-γ receptor gene.