Analysis of the effect of S mansomi infection on regulatory T cell development and function

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The immune response to antigen is regulated in a variety of ways including by regulatory T cells (T regs). An over exuberant immune response to antigen can be detrimental and could cause tissue damage. Following infection with a helminth such as S. mansoni there is good evidence to show that immune responses are dampened down. For example, it has been shown that allergic responses are diminished and also that autoimmunity, where the immune system destroys self tissue, is inhibited. We and others have shown that following exposure to S. mansoni antigens T regs are induced. NOD mice have been shown to have defects in T reg function and this might represent one of the predisposing features for development in autoimmunity. We find that following exposure to S. mansoni antigens there is an increase in T cell production of IL-10, a marker of T reg activity. Naturally arising and induced T regs have different functional characteristics and it is unclear whether the T regs induced by S. mansoni fall into both categories or only one of them. Regulatory T cells are known not oly to be induced by IL-10 but also TGFbeta both of which are elicited in the mammalian host by exposure to schistosomal antigens. We propose to characterise the T regs induced during infection with S. mansoni and exposure to schistosome antigens in normal mice and in NOD mice with their known defects in T reg activity. In this way we will be able to define not only the mechanisms by which this induction of T regs occurs but also have the potential to identify schistosome derived molecules mediating this effect. This could lead to the identification of novel biomodulators that might have potential in the treatment of inflammatory conditions such as autoimmunity and inflammatory bowel disease.