Allergic diseases such as asthma, rhinitis, and eczema are increasing in prevalence and affect about 15% of the population in countries such as the UK or USA. Regulatory T cells (TRegs) have been shown to be critical in the maintenance of immune responses and T cell homeostasis. For example, depletion of CD4+CD25+ TRegs from mice resulted in the development of multiorgan autoimmune diseases. So-called ‘natural’ CD4+CD25+ TRegs and/or IL-10-producing Tr-1 cells are capable of suppressing Th2 responses to allergens in health, whereas such inhibition is attenuated in allergic conditions. In this context, both cell-cell contact-dependent (either through membrane bound TGF-β or via suppressive molecules such as CLTA-4) and soluble cytokine- (TGF-β and IL-10) dependent mechanisms have been shown to contribute to the function of TRegs. Moreover, adoptive transfer of CD4+CD25+ TRegs from healthy to diseased animals resulted in the prevention or cure of certain autoimmune diseases, and was able to induce transplantation tolerance. Clinical improvement seen after allergen immunotherapy for allergic diseases such as rhinitis and asthma is associated with the induction of IL-10 & TGF-β producing Tr-1 cells as well as Foxp3 expressing IL-10 T cells, with resulting suppression of the Th2 cytokine milieu. Activation and expansion of antigen-specific CD4+CD25+ TRegs in vivo using adjuvants or pharmacological agents such as low dose steroids or vitamin D3 could represent novel approaches to induce antigen-specific tolerance in human diseases including allergic asthma, autoimmune disease and the rejection of transplanted organs.
Keywords: Allergic diseases, asthma, rhinitis, homeostasis, T cells, autoimmune diseases, cytokine, immunotherapy
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