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

From the ^* Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington, Connecticut 06037; the 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 β7 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 β7 integrins or only the Eβ7 integrin. To quantitate the relative use of β7 integrins in migration in vivo, equal numbers of OT-I and OT-I-β7^–/– or OT-I-E^–/– lymph node (LN) cells were adoptively transferred to normal mice. Although OT-I-β7^–/– LN cells migrated to mesenteric LN and peripheral LN as well as wild-type cells, β7 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, β7 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 β7 integrin–mediated. The Eβ7 integrin appeared to play no role in migration during a primary CD8 T cell immune response in vivo. Furthermore, despite dramatic upregulation of Eβ7 by CD8 T cells after entry into the epithelium, long-term retention of intestinal intraepithelial lymphocytes was also Eβ7 independent.

Key Words: migration • mucosa • integrins • activation • CD8

Abbreviations used: DCs, dendritic cells; IEL, intraepithelial lymphocyte; LP, lamina propria; MLNs, mesenteric lymph nodes; PLN, peripheral lymph node; PPs, Peyer's patches; VSV-ova, vesicular stomatitis virus encoding ovalbumin.

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