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J. Exp. Med., Volume 189, Number 10, May 17, 1999 1631-1638

The Role of beta 7 Integrins in CD8 T Cell Trafficking During an Antiviral Immune Response

By Leo Lefrançois,* Christina M. Parker,Dagger Sara Olson,* Werner Muller,§ Norbert Wagner,§ and Lynn Puddington*

From the * Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington, Connecticut 06037; the Dagger  Lymphocyte Biology Section, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and the § Institute for Genetics, University of Cologne, 50937 Cologne, Germany

The requirement of beta 7 integrins for lymphocyte migration was examined during an ongoing immune response in vivo. Transgenic mice (OT-I) expressing an ovalbumin-specific major histocompatibility complex class I-restricted T cell receptor for antigen were rendered deficient in expression of all beta 7 integrins or only the alpha Ebeta 7 integrin. To quantitate the relative use of beta 7 integrins in migration in vivo, equal numbers of OT-I and OT-I-beta 7-/- or OT-I-alpha E-/- lymph node (LN) cells were adoptively transferred to normal mice. Although OT-I-beta 7-/- LN cells migrated to mesenteric LN and peripheral LN as well as wild-type cells, beta 7 integrins were required for naive CD8 T cell and B cell migration to Peyer's patch. After infection with a recombinant virus (vesicular stomatitis virus) encoding ovalbumin, beta 7 integrins became critical for migration of activated CD8 T cells to the mesenteric LN and Peyer's patch. Naive CD8 T cells did not enter the lamina propria or the intestinal epithelium, and the majority of migration of activated CD8 T cells to the small and large intestinal mucosa, including the epithelium, was beta 7 integrin-mediated. The alpha Ebeta 7 integrin appeared to play no role in migration during a primary CD8 T cell immune response in vivo. Furthermore, despite dramatic upregulation of alpha Ebeta 7 by CD8 T cells after entry into the epithelium, long-term retention of intestinal intraepithelial lymphocytes was also alpha Ebeta 7 independent.

Key words: migration;  mucosa;  integrins;  activation;  CD8


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