Because TRECs are stable within the original T cell and do not duplicate during mitosis they are diluted out in the periphery with antigen-driven or homeostatic
cell division . However, in healthy individuals, only homeostatic proliferation of naive T cells is likely to affect peripheral T cell TREC content significantly, as antigen-induced T cell proliferation will, to the most extent, affect memory/antigen-primed T cells with very minute amounts of TRECs, and thus not the population of RTE. Nevertheless, to exclude that the reduced TREC concentrations in peripheral blood lymphocytes from several UC patients, as well as CD patients, were caused by an increased peripheral T cell turnover we determined the frequencies buy VX-770 of proliferating T lymphocytes, detected as Ki67+CD3+ T lymphocytes, and found the prevalence to be equivalent in IBD patients and healthy individuals. Supporting the notion that the reduced TREC levels in peripheral blood T cells in several IBD patients are not caused by extensive proliferation
was also the finding of comparable frequencies of CD45RA+ as well as CD62L+ T lymphocytes in peripheral blood from IBD patients and healthy individuals. Thus, a likely explanation to the reduced TREC levels in peripheral blood from IBD patients could be Selleck 3-MA enhanced migration of RTE from the blood to the inflamed mucosa, purging the peripheral blood of this population. The purpose of separating the integrin β7+ lymphocytes in peripheral blood was to analyse if there was a direct recruitment of gut homing T cells from the thymus.
The fact that the integrin β7+ population did not differ from unseparated lymphocytes regarding TREC content indicate that the majority of peripheral blood lymphocytes have divided, irrespective of integrin of β7+ expression. Although the frequency Succinyl-CoA of proliferating T lymphocytes was not estimated in the intestinal mucosa, the proliferation rate in UC patients would be increased rather than decreased compared to controls, due to the chronic inflammation. Thus, if anything, we are underestimating the amount of TRECs in mucosal lymphocytes of IBD patients by not expressing it relative to the proliferation rate of the T lymphocytes. Splitting the patient group into those with active disease versus those with inactive disease demonstrated that this recruitment was not limited to the actively inflamed mucosa, indicating a constant influx of RTE to the intestinal mucosa in UC patients also during remission. It would be very interesting to investigate the role of these RTE for the disease course, e.g.