Oral tolerance is one of the hallmarks of intestinal immunity that induces systemic unresponsiveness to orally ingested antigens. Beta 7 integrin is known to mediate lymphocyte migration to gut-associated lymphoid tissues, especially Peyer’s patches. We assume that lack of beta 7 integrin might affect oral tolerance due to defective lymphocyte migration to intestinal tissues. When mice were intraperitoneally immunized with OVA following oral OVA administration, beta 7 integrin deficient mice showed defective oral tolerance measured by OVA-specific IgG and IgM antibody titers, numbers of OVA-specific antibody forming cells, and proliferative responses to OVA. Oral tolerance in L-selectin deficient mice was unimpaired. Moreover, beta 7 integrin/ L-selectin double deficient mice showed defective oral tolerance to a similar degree as beta 7 integrin deficient mice, suggesting no additive effect of L-selectin deficienty. We also measured cytokine secretion from splenocytes following oral tolerance induction and found that whereas IFN gamma secretion was decreased in wild-type mice, this reduction was abrogated in beta 7 deficient mice. These results demonstrate that beta 7 integrin is essential for oral tolerance.
- Copyright © 2011 by The American Association of Immunologists, Inc.