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

J Clin Invest. 2000 Dec;106(12):1541-52. doi: 10.1172/JCI10927.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

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