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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.
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Article

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

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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

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Figure 2

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RV shedding of β7–/– mice depleted of CD8+ T cells with mAb. The effect ...
RV shedding of β7–/– mice depleted of CD8+ T cells with mAb. The effect of anti-CD8 mAb treatment on CD8+ T-cell populations and rotaviral shedding is shown. (a) Flow cytometry data indicating CD8+ αβ T-cell populations in different tissues of β7–/– and wt mice that were treated or untreated with anti-CD8 mAb. β7–/– mice were depleted of CD8+ T cells and subsequently infected with RV as described in Methods. At day 25 from the beginning of the experiment, the mice were sacrificed and IEL, MLNs, and spleen cells were purified, stained with anti-CD8 and anti-TCRαβ antibodies, and analyzed by FACS. (b) Stool samples were collected daily following RV infection, and the levels of RV Ag were determined by ELISA. SD is based on four animals per group (the figure represents one out of two experiments performed with similar results).

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