Alteration of Vβ Usage and Cytokine Production of CD4+ TCR ββ Homodimer T Cells by Elimination of Bacteroides vulgatus Prevents Colitis in TCR α-Chain-Deficient Mice

Abstract

A major pathogenic factor for the development of inflammatory bowel disease (IBD) is the breakdown of the intestinal homeostasis between the host immune system and the luminal microenvironment. To assess the potential influence of luminal Ags on the development of IBD, we fed TCR α−/− mice an elemental diet (ED). ED-fed TCR α−/− mice showed no pathologic features of IBD, and their aberrant mucosal B cell responses were suppressed. Similar numbers of CD4+, TCR ββ homodimer T cells (ββ T cells) were developed in the colonic mucosa of ED-fed mice; however, Th2-type cytokine productions were lower than those seen in diseased regular diet (RD)-fed mice. The higher cytokine production in diseased RD-fed mice could be attributed to the high incidence of Bacteroides vulgatus (recovered in 80% of these mice), which can induce Th2-type responses of colonic CD4+, ββ T cells. In contrast, ED-fed TCR α−/− mice exhibited a diversification of Vβ usage of ββT cell populations from the dominant Vβ8 one associated with B. vulgatus in cecal flora to Vβ6, Vβ11, and Vβ14. Rectal administration of disease-free ED-fed mice with B. vulgatus resulted in the development of Th2-type CD4+, ββ T cell-induced colitis. These findings suggest that the ED-induced alteration of intestinal microenvironments such as the enteric flora prevented the development of IBD in TCR α−/− mice via the immunologic quiescence of CD4+, ββ T cells.

Faecal microbiota profile of Crohn’s disease determined by terminal restriction fragment length polymorphism analysis

“…The presence of intestinal bacteria is essential for the development of experimental colitis in several animal models. [8][9][10] In CD, faecal stream diversions reduce gut inflammation and induce mucosal healing in excluded intestinal segments, whereas infusions of intestinal contents rapidly provoke disease flare-ups.…”

Diversity of caecal bacteria is altered in interleukin-10 gene-deficient mice before and after colitis onset and when fed polyunsaturated fatty acids

“…These species have been detected in colitis models (Rath et al, 1999) and in human IBD patients (Swidsinski et al, 2005). Although B. vulgatus is known to be associated with colitis (Rath et al, 1999;Kishi et al, 2000), mono-colonization of germ-free Il10 -/-mice with B. vulgatus did not lead to colitis (Kim et al, 2007), indicating the importance of bacterial community composition in the induction of colitis in a genetically susceptible host.…”

New Insights into Mechanism of Inflammatory and Allergic Diseases in Mucosal Tissues

“…The TCRα mutant mice that were fed an elemental diet (ED) consisting of chemically defined amino acids without any antigenic molecules exhibited the complete loss of murine colitis, while TCRα mutant mice fed a nutritional regular diet (RD) spontaneously developed a typical IBD [12]. The levels of mucosal IgA responses developed in ED-fed non-diseased mice were strikingly reduced when compared with RD-fed mice with IBD.…”

“…In this context, the influence of diet for the development of mucosal inflammation was also assessed in this murine model [12]. The TCRα mutant mice that were fed an elemental diet (ED) consisting of chemically defined amino acids without any antigenic molecules exhibited the complete loss of murine colitis, while TCRα mutant mice fed a nutritional regular diet (RD) spontaneously developed a typical IBD [12].…”