| Summary: | The intestinal IgA response has features that are different to those of the systemic humoral response, which is dominated by IgG. Although the IgA response, like the IgG response, includes an antigen specific component, it is also associated with polyspecificity and autoimmunity. The profile of intestinal immunoglobulins changes in inflammatory bowel disease (IBD) where there is a disproportionate increase in IgG production and in ulcerative colitis (UC), this includes the production of autoantibodies. In this thesis, two immunoregulatory T cell subsets that could influence the intestinal B cell response have been studied; T follicular helper cells (TFH) and regulatory T cells (Treg). Results in chapter 3 show that there is a higher density of TFH in gut associated lymphoid tissue (GALT) compared to peripheral lymphoid tissue due to a higher density of CD57- TFH- The expression of cytokines and CD40L was almost comparable between CD57+ and CD57- TFH- However, culturing experiments suggest that CD57-TFH may develop into CD57+ TFH and there is a constant turnover of TFH in the gut. Experiments in chapter 4 attempted to seek evidence for a developmental relationship between TFH and Treg by analysis of T cell receptor sequences. No evidence of plasticity between these subsets was observed. Experiments in chapter 5 set out to characterise TFH in IBD. In the appendix of UC patients, nearly all TFH were CD57+ and at a high density within germinal centres (GC). This thesis concludes that TFH are more phenotypically diverse and denser in GALT compared to peripheral lymphoid tissue. This may reduce the threshold for GC B cell survival in the gut permitting the propagation of plasma cells that secrete polyspecific and autoreactive IgA. TFH are denser still in the small GC in UC appendix. This may be relevant to the production of autoantibodies and disease pathogenesis.
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