alpha(4)beta(7) independent pathway for CD8+ T cell-mediated intestinal immunity to rotavirus

Rotavirus (RV), which replicates exclusively in cells of the small intestin e, is the most important cause of severe diarrhea in young children worldwi de. Using a mouse model, we show that expression of the intestinal homing i ntegrin 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 expressio n (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 cel ls in beta7(-/-) animals prolonged viral shedding, and transfer of immune b eta7(-/-) CD8(+) T cells into chronically infected Rag-2-deficient mice res olved RV infection as efficiently as wt CD8(+) T cells. Paradoxically, alph a (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) C D8(+) T cells. We explained this apparent contradiction by demonstrating th at expression of alpha (4)beta (7) on effector CD8(+) T cells depends upon the site of initial antigen exposure: oral immunization generates RV-specif ic CD8(+) T cells primarily of an alpha (4)beta (hi)(7) phenotype, but subc utaneous immunization yields both alpha (4)beta (hi)(7) and alpha (4)beta ( low)(7) immune CD8(+) T cells with anci-RV effector capabilities. Thus, alp ha (4)beta (7) facilitates normal intestinal immune trafficking to the gut, but it is not required for effective CD8(+) T cell immunity.