Active induction of allergen specific Th1 cells for atopic asthma

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In type 1 allergic diseases, allergen specific Th2 cells are differentiated and play central roles on the formation of IgE responsiveness, organ hyper-reactivity and allergic inflammation.In this study what determinants might be responsible for such differentiation and whether induction of allergen specific Th1 cells through active immunization caused an inhibition of development of type 1 allergic diseases was asked.The expression of cytokine and polymorphisms of candidate genes, which might lead to preferential Th2 differentiation were examined.In the patients with atopic dermatitis it was found that IL-6 was over-produced by peripheral monocytes and serum level of IL-18 was elevated.To reveal whether or not these cytokines would function in the T cell differentiation, IL-6 gene knock-out mice or atopic dermatitis-model mice was employed.The results indicate that these cytokines are negative regulatory cytokines in the Th2 development.Analyses of gene polymorphisms including 5" IL-4 regulatory region, IL-4 receptor and beta2-adrenoceptor exon genes showed that each polymorphism by itself might not be related to atopic diseases.However, it is possible that the combination of gene polymorphisms relate to the onset of the diseases, which are now in progress.After screening, one low molecular weight non-peptide compound was found to inhibit IL-4 signalling such as IL-4-induced Th2 differentiation and IL-4-induced IgE synthesis by mouse and human lymphocytes.Even in vivo, an administration of this one suppressed IgE synthesis and eosinophil number in BALE in asthmatic model mice.Thus it was a novel anti-allergic compound.NC/Nga mice, spontaneously developed atopic dermatitis model mice, were sensitized with House Dust (HD) mite.Whether active induction of HD mite-specific Th1 cells in vivo before the clinical onset of the disease lead to suppression of the development of dermatitis and of IgE elevation is now tested.