α4β7 independent pathway for CD8+ T cell-mediated intestinal immunity to rotavirus

Rotavirus (RV), which replicates exclusively in cells of the small intestine, is the most important cause of severe diarrhea in young children worldwide. Using a mouse model, we show that expression of the intestinal homing integrin alpha (4)beta (7) is not essential for CD8(+) T cells to migrate to the intestine or provide immunity to RV. Mice deficient in beta7 expression (beta7(-/-)) and unable to express alpha (4)beta (7) integrin were found to clear RV as quickly as wild-type (wt) animals. Depletion of CD8(+) T cells in beta7(-/-) animals prolonged viral shedding, and transfer of immune beta7(-/-) CD8(+) T cells into chronically infected Rag-2-deficient mice resolved RV infection as efficiently as wt CD8(+) T cells. Paradoxically, alpha (4)beta (hi)(7) memory CD8(+) T cells purified from wt mice that had been orally immunized cleared RV more efficiently than alpha (4)beta (low)(7) CD8(+) T cells. We explained this apparent contradiction by demonstrating that expression of alpha (4)beta (7) on effector CD8(+) T cells depends upon the site of initial antigen exposure: oral immunization generates RV-specific CD8(+) T cells primarily of an alpha (4)beta (hi)(7) phenotype, but subcutaneous immunization yields both alpha (4)beta (hi)(7) and alpha (4)beta (low)(7) immune CD8(+) T cells with anci-RV effector capabilities. Thus, alpha (4)beta (7) facilitates normal intestinal immune trafficking to the gut, but it is not required for effective CD8(+) T cell immunity.