Efficient lymphocyte migration across high endothelial venules of mouse Peyer's patches requires overlapping expression of l-selectin and beta(7) integrin

Lymphocyte migration into lymphoid organs is regulated by adhesion molecule s including L-selectin and the beta(7) integrins, L-selectin and alpha(4)be ta(7) are predominantly hypothesized to direct the selective migration of l ymphocytes to peripheral lymph nodes and the gut-associated lymphoid tissue s, respectively, To further characterize interactions between L-selectin an d beta(7) integrins during lymphocyte recirculation, mice deficient in both receptors (L-selectin/beta(7) integrin(-/-)) were generated, The simultane ous loss of L-selectin and beta(7) integrin expression prevented the majori ty of lymphocytes( >95% inhibition) from attaching to high endothelial venu les (HEV) of Peyer's patches and other lymphoid tissues during in vitro bin ding assays. Moreover, the inability to bind HEV eliminated the vast majori ty of L-selectin/beta(7) integrin(-/-) lymphocyte migration into Peyer's pa tches during short-term and long-term in vivo migration assays (>99% inhibi tion,p < 0.01). The lack of lymphocyte migration into Peyer's patches corre lated directly with the dramatically reduced size and cellularity (99% redu ced) of this tissue in L-selectin/beta(7) integrin(-/-) mice. High numbers of injected L-selectin/beta(7) integrin(-/-) lymphocytes remaining in the b lood of wild-type mice correlated with markedly increased numbers of circul ating lymphocytes in L-selectin/beta(7) integrin(-/-) mice, Loss of either L-selectin or the beta(7) integrins alone resulted in significant but incom plete inhibition of Peyer's patch migration. Collectively, the phenotype of L-selectin/beta(7) integrin(-/-) mice demonstrates that these two receptor s primarily interact along the same adhesion pathway that is required for t he vast majority of lymphocyte migration into Peyer's patches.