Alteration of V beta Usage and Cytokine Production of CD4 super(+) TCR beta beta Homodimer T Cells by Elimination of Bacteroides vulgatus Prevents Colitis in TCR alpha -Chain-Deficient Mice

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 alpha super(-/-) mice an elemental diet (ED). ED-fed TCR alpha super(-/-) mice showed no pathologic features of IBD, and their aberrant mucosal B cell responses were suppressed. Similar numbers of CD4 super(+), TCR beta beta homodimer T cells ( beta beta 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 super(+), beta beta T cells. In contrast, ED-fed TCR alpha super(-/-) mice exhibited a diversification of V beta usage of beta beta T cell populations from the dominant V beta 8 one associated with B. vulgatus in cecal flora to V beta 6, V beta 11, and V beta 14. Rectal administration of disease-free ED-fed mice with B. vulgatus resulted in the development of Th2-type CD4 super(+), beta beta 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 alpha super(-/-) mice via the immunologic quiescence of CD4 super(+), beta beta T cells.