L-selectin and beta7 integrin synergistically mediate lymphocyte migration to mesenteric lymph nodes.

Mesenteric lymph nodes (MLN) drain the gut where nutritive antigens and pathogens are encountered by lymphocytes of the gut-associated lymphoid tissue. We sought to determine how lymphocytes enter the MLN by studying mice double deficient for beta7 integrins and L-selectin. beta7/L-selectin double-deficient lymphocytes did not migrate into MLN. Most importantly, MLN formation was drastically impaired in beta7/L-selectin double-deficient mice. Lymphocyte numbers in MLN from beta7/L-selectin double-deficient mice were tenfold reduced compared to control mice. A high percentage of the few lymphocytes still detected in MLN from beta7/L-selectin double-deficient mice were CD44hi CD18hi, suggesting alternate migration pathways independent of L-selectin and beta7 integrin for these cells. We conclude that the combination of both molecules, L-selectin and beta7 integrin, is indispensable for MLN formation and that these molecules may mediate lymphocyte migration to MLN in a sequential and synergistical manner.