The development of Autoimmune-diseases antigen-specific therapy by the induction of regulatory T cells transcription factors

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CD4+CD25+ regulatory T cells control homeostasis of immune system. The decrease of this population in number has been demonstrated to result in the development of autoimmune diseases, whereas the suppression of this population has been demonstrated to elicit effective immune response to tumors. Therefore, if we are able to control the number and activity of the regulatory T cells, we may develop an innovative immunotherapy. Although we as well as others found that this population arises from self-reactive CD4+ T cells in the thymus, the precise mechanism of their development remained elusive. Since it has been demonstrated that transcription factors specific for each T helper subset are able to control the differentiation of the subsets, we decided to find transcription factors which are involved in the development of the regulatory T cells.We conducted subtractive cDNA cloning using mRNAs from CD4+CD25+ regulatory T cells and CD4+CD25- conventional T cells. We have cloned a number of unknown cDNA clones as well as the cDNA clones corresponding to CD25, CTLA4, OX40, TLR4 and etc. those which are already known to be specific for regulatory T cells. Among the unknown clones, we have identified two cDNA clones ; the one was supposed to regulate redox and found to suppress IL-2 production and apoptosis. The other was supposed to be a transcription factor. When we overexpress this molecule in the conventional T cells, the transduced T cells stopped proliferation, suggesting that the supposed-to-be transcription factor might regulate cell proliferation or IL-2 production, both of which need to be controlled in the regulatory T cells. Due to the proliferation deficiency, we are not able to confirm their phenotype. We now con duct further investigation to reveal the mechanism of the transcription factor.