Establishment of antigen-specific regulatory T cell lines induced by oral tolerance and the application to immunotherapy

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Oral tolerance is one of the promising methods for immunotherapy. Regulatory T cells generated by the orally administered antigens would be the most responsible cell population for the suppressive action. In order to establish regulatory T cell lines, it is important to know the mechanisms of the regulation as well as the conditions to generate these T cells. We thus establish an assay system to monitor the suppressive activity to the ongoing immune-response by mixing the candidate regulatory cells with antigen-specific splenocytes. We next focused on the Th3/Tr1 cells which secrete TGF-beta because this cells is one of the most well characterized regulatory cells. We have thus characterize the several culture conditions to generate Th3/Tr1 cells. Spleen cells from OVA specific TCR transgenic mice were cultured in different conditions and resultant OVA specific cells were assayed for the secretion of TGF-beta or the above established evaluation system. We are now narrowing down suitable conditions for the generation of regulatory cells.