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
D. Kishi et al., 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, J IMMUNOL, 165(10), 2000, pp. 5891-5899
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.