The presence of a significantly increased number of TCR Vβ8+ lymphocytes in Peyer’s patches upon chronic DSS-induced colitis

is associated with aggravated mucosal inflammation, as determined by significantly increased weight loss and MEICS score of Bim–/– compared to wild-type mice. Data from spleen weight, colon length and histological score confirmed this suggestion. Interestingly, TCR Vβ8+ lymphocytes can bind SEB. Wild-type mice treated with a single intrarectal instillation of SEB displayed a time- and dose-dependent colonic inflammation which was further increased significantly in ovalbumin transgenic mice with 95% TCR Vβ8+ lymphocytes [24]. Enhanced expression of the pro-survival proteins BCL-2 and BCL-xL was determined in PD98059 supplier lamina propria T cells of patients with CD when compared with controls. Lamina propria T cells in CD patients show activation of the STAT-3 signalling pathway mediated by IL-6. Activation of STAT-3 is followed by the induction of anti-apoptotic genes such as BCL-2 and BCL-xL [14]. Resistance of CD T cells to multiple apoptotic signals is associated with increased BCL-2 expression. An abnormal BCL-2 expression in lamina propria mononuclear cells from patients with CD was demonstrated [15]. A significantly higher BCL-2/Bax ratio in CD mucosa compared to controls was reported [16]. These data are consistent

with a recent report showing significant resistance to Fas-induced apoptosis of peripheral T cells from CD patients

[17]. The same immunological consequence resulting from the extended lifespan of antigen-primed T cells is PI3K Inhibitor Library supported by a reduced survival or function of Treg cells. Apoptosis is elevated strongly in mucosal and peripheral CD4+CD25highforkhead box protein 3 (FoxP3)+ Treg cells of patients with IBD [25]. Failure of the apoptotic mechanism of lymphocyte control can lead to the development of autoimmunity or lymphoma. Bim deficiency perturbed thymic T cell development. As expected for the loss of a pro-apoptotic molecule, PTK6 the numbers of both the CD4−8− pro-T cells and the mature T cells (CD4+8− and CD4−8+) were two- to threefold higher than in wild-type animals. Surprisingly, however, the CD4+8+ pre-T cells, the predominant thymic subpopulation, were only half the normal level [8]. Interestingly, we observed rectum prolapses in Bim–/– animals. The trigger for the appearance of prolapses was not investigated in this work. As described for mice homozygous for Il10tm1Cgn, targeted mutations leading to altered lymphocyte populations are most likely to be involved in prolapse formation. As described for IL-10–/– mice, animal housing conditions and the microbiome influence prolapse development. However, our mice were housed in IVC in a SPF facility where a less developed microbiome could be expected. We found significantly increased inflammation in Bim–/– animals compared to wild-type mice upon chronic DSS-induced colitis.