α4β7 independent pathway for CD8+ T cell–mediated intestinal immunity to rotavirus
Nelly A. Kuklin, … , Eugene C. Butcher, Harry B. Greenberg
Nelly A. Kuklin, … , Eugene C. Butcher, Harry B. Greenberg
Published December 15, 2000
Citation Information: J Clin Invest. 2000;106(12):1541-1552. https://doi.org/10.1172/JCI10927.
View: Text | PDF
Article

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

Abstract

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 α4β7 is not essential for CD8+ T cells to migrate to the intestine or provide immunity to RV. Mice deficient in β7 expression (β7–/–) and unable to express α4β7 integrin were found to clear RV as quickly as wild-type (wt) animals. Depletion of CD8+ T cells in β7–/– animals prolonged viral shedding, and transfer of immune β7–/– CD8+ T cells into chronically infected Rag-2–deficient mice resolved RV infection as efficiently as wt CD8+ T cells. Paradoxically, α4β7hi memory CD8+ T cells purified from wt mice that had been orally immunized cleared RV more efficiently than α4β7low CD8+ T cells. We explained this apparent contradiction by demonstrating that expression of α4β7 on effector CD8+ T cells depends upon the site of initial antigen exposure: oral immunization generates RV-specific CD8+ T cells primarily of an α4β7hi phenotype, but subcutaneous immunization yields both α4β7hi and α4β7low immune CD8+ T cells with anti-RV effector capabilities. Thus, α4β7 facilitates normal intestinal immune trafficking to the gut, but it is not required for effective CD8+ T cell immunity.

Authors

Nelly A. Kuklin, Lusijah Rott, Jama Darling, James J. Campbell, Manuel Franco, Ningguo Feng, Werner Müller, Norbert Wagner, John Altman, Eugene C. Butcher, Harry B. Greenberg

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Fecal rotaviral Ag shedding in Rag-2 mice chronically infected with RV f...
Fecal rotaviral Ag shedding in Rag-2 mice chronically infected with RV following adoptive transfer of varying numbers of immune β7–/– or wt CD8+ splenic T cells. Donor mice were immunized orally as described in Methods, and spleen cells from these donor mice were harvested 30 days after immunization. (a) Ag shedding in RV-infected Rag-2 mice not transferred with cells. (b and c) RV Ag shedding of Rag-2 mice transferred with 5 × 103 CD8+ T cells. (d and e) RV Ag shedding of Rag-2 mice transferred with 5 × 104 CD8+ T cells. (f and g) RV Ag shedding of Rag-2 mice transferred with 5 × 105 CD8+ T cells. Asterisks represent RV Ag shedding in chronically infected Rag-2 mice that did not receive immune cells (a). Open circles represent RV shedding in Rag-2 mice adoptively transferred with β7–/– CD8+ T cells (b, d, and f). Filled circles represent RV shedding in Rag-2 mice adoptively transferred with wt CD8+ T cells (panels c, e, and g).