Intestinal Bifidobacterium association in germ-free T cell receptor transgenic mice down-regulates dietary antigen-specific immune responses of the small intestine but enhances those of the large intestine.

Bifidobacterium is a dominant bacterial species among commensals in the human intestine and is thought to have probiotic immunomodulatory effects. In this study, we investigated the effect of the association with Bifidobacterium pseudocatenulatum JCM 7041 (Bp) on dietary ovalbumin (OVA)-specific immune responses using germ-free OVA-specific T cell receptor transgenic mice (OVA23-3 mice). We established germ-free OVA23-3 mice, and then associated with Bp (BIF group) or without (CONT group) and additionally associated with segmented filamentous bacteria (SFB) and clostridia in both groups. BIF and CONT mice were fed an egg-white diet containing OVA for 1 week. Cytokine production in response to OVA by cells of Peyer's patches (PPs) and lamina propria (LP) from the small and large intestine was measured. Interferon (IFN)-gamma and interleukin (IL)-6 production by PP cells from BIF group mice was lower than that of the CONT group. The proportion of PP cells expressing CD4+CD62L(low), an activated/memory T cell phenotype, was higher in BIF group mice than the CONT group. Furthermore, LP cells from the small intestine in Bp-associated mice showed a tendency to produce slightly lower IFN-gamma and IL-6, while the cells from large intestine produced markedly higher IFN-gamma, IL-5 and IL-6 than those in the CONT group. The pattern of cytokine production by PP in BIF animals was similar to those isolated from conventional mice. These results suggest that intestinal association with Bp might down-regulate excessive immune responses to dietary antigens of the small intestine but enhance those of the large intestine.