Alteration of V beta usage and cytokine production of CD4(+) TCR beta betahomodimer 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 immu ne system and the luminal microenvironment. To assess the potential influen ce of luminal Ags on the development of IBD, we fed TCR alpha (-/-) mice an elemental diet (ED), ED-fed TCR alpha (-/-) mice showed no pathologic feat ures of IBD, and their aberrant mucosal B cell responses were suppressed. S imilar numbers of CD4(+), TCR beta beta homodimer T cells (beta beta T cell s) were developed in the colonic mucosa of ED-fed mice; however, Th2-type c ytokine 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 ran induce Th2-type responses of colonic CD4(+), bet a beta T cells. In contrast, ED-fed TCR alpha (-/-) mice exhibited a divers ification of V beta usage of PPT cell populations from the dominant V beta8 one associated with B, vulgatus in cecal flora to V beta6, V beta 11, and V beta 14, Rectal administration of disease-free ED-fed mice with B, vulgat us resulted in the development of Th2-type CD4(+), beta beta T cell-induced colitis. These findings suggest that the ED-induced alteration of intestin al microenvironments such as the enteric flora prevented the development of IBD in TCR alpha (-/-) mice via the immunologic quiescence of CD4(+), beta beta T cells.