The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction.

The role of intestinal bacterial flora in oral tolerance induction to the IgE response was investigated using germfree (GF) mice. When GF mice were orally administered 20 mg of OVA as tolerogen before a systemic challenge with OVA, the Th1-mediated responses, such as the production of IgG2a and IFN-gamma, were abrogated, while the Th2-mediated immune responses, such as the production of IgE, IgG1, and IL-4, were maintained. Moreover, the basal level of IL-4 production in vitro was significantly higher in the GF mice than that of IL-4 in specific pathogen-free mice when challenged systemically with OVA. On the other hand, both Th1 and Th2 responses were fully sensitive to such tolerance induction in specific pathogen-free mice. The reconstitution of intestinal flora of GF mice with Bifidobacterium infantis, one of the predominant bacteria in the intestinal flora, restored the susceptibility of these Th2 responses to oral tolerance induction; however, this was only effective when such reconstitution was performed in neonates, but not in mice at an older age. These results thus suggested that intestinal bacterial flora play a crucial role in generating a Th2 cell population whose size and response are adequately regulated and, consequently, fully susceptible to oral tolerance induction, probably by affecting the development of gut-associated lymphoid tissue at the neonatal stage.