alpha(4)beta(7) 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 alpha(4)ss(7) is not essential for CD8(+) T cells to migrate to the intestine or provide immunity to RV. Mice deficient in ss7 expression (ss7(-/-)) and unable to express alpha(4)ss(7) integrin were found to clear RV as quickly as wild-type (wt) animals. Depletion of CD8(+) T cells in ss7(-/-) animals prolonged viral shedding, and transfer of immune ss7(-/-) CD8(+) T cells into chronically infected Rag-2-deficient mice resolved RV infection as efficiently as wt CD8(+) T cells. Paradoxically, alpha(4)ss(7)(hi) memory CD8(+) T cells purified from wt mice that had been orally immunized cleared RV more efficiently than alpha(4)ss(7)(low) CD8(+) T cells. We explained this apparent contradiction by demonstrating that expression of alpha(4)ss(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)ss(7)(hi) phenotype, but subcutaneous immunization yields both alpha(4)ss(7)(hi) and alpha(4)ss(7)(low) immune CD8(+) T cells with anti-RV effector capabilities. Thus, alpha(4)ss(7) facilitates normal intestinal immune trafficking to the gut, but it is not required for effective CD8(+) T cell immunity.

• Authors: N A Kuklin, L Rott, J Darling, J J Campbell, M Franco, N Feng, W Müller, N Wagner, J Altman, E C Butcher, H B Greenberg
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 106 Issue 12 Pg. 1541-52 (Dec 2000) ISSN: 0021-9738 [Print] United States
• PMID: 11120761 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• DNA-Binding Proteins
• Immunoglobulin A
• Integrins
• Rag2 protein, mouse
• V(D)J recombination activating protein 2
• integrin alpha4beta7
• Interferon-gamma

Topics

• Adoptive Transfer
• Animals
• Antibodies, Monoclonal (immunology)
• CD8-Positive T-Lymphocytes (immunology, transplantation)
• Chemotaxis, Leukocyte
• DNA-Binding Proteins (genetics, physiology)
• Feces (virology)
• Flow Cytometry
• Gene Deletion
• Immunoglobulin A (immunology)
• Immunohistochemistry
• Integrins (genetics, physiology)
• Interferon-gamma (metabolism)
• Intestine, Small (immunology, virology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Rotavirus (immunology, physiology)
• Rotavirus Infections (immunology, virology)
• Spleen (cytology, immunology)
• Virus Shedding