Elucidation of functional mechanisms of intestinal immune regulatory cells and recovery of immune function by foods using these cells as targets

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1. Analysis of intestinal cell populations that induce IgA production from B cells Intestinal IgA production is first line defense against infection. Therefore, cells that augment IgA production are targets for immuno-modulation by foods. We had identified Peyer's patch (PP) CD3-IL-2R^+ cells as a non-T non-B cell population producing high level of IL-5, and promoting IgA production in vitro. Expression of the microbial receptor TLRs in these cells, response of these cells to poly I:C (model ligand for virus RNA), and cell function in germ free mice were analyzed. The results suggested that CD3-IL-2R^+ cells recognize microbial components and virus infection and promote IgA production in the intestine. Further it was implied that CD3-IL-2R^+ cells are stimulated in PP and then migrate to the lamina propria. In addition, we examined the response of PP dendritic cells to TLR ligand stimuli, and obtained results which suggested that intestinal dendritic cells mediate B-cell independent IgA production against microbes through production of factors such as IL-6.2. Analysis of regulatory T cells in oral tolerance Oral tolerance is a suppressive mechanism for food allergy. Regulatory T cells in oral tolerance are good targets for immuno-modulation. CD62L^high/int CD44^intT cells and CD62L^lowCD44^highT cells were induced by oral administration of ovalbumin (OVA) in DO11.10 OVA-specific TCR transgenic mice. Both populations were anergic and possessed regulatory function. CD62L^low CD44^highT cells possessed stronger suppressive function, and induced apoptosis to co-cultured naive T cells effectively. Our results taken together demonstrate CD62L^high/int CD44^intT cells and CD62L^low CD44^highT cells are induced in oral tolerance, and each expressed different types of regulatory function.