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© The Rockefeller University Press, 0022-1007/1999/5/1631/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 10, May 17, 1999 1631-1638

Articles

The Role of β7 Integrins in CD8 T Cell Trafficking During an Antiviral Immune Response

Leo Lefrançois*, Christina M. Parker{ddagger}, Sara Olson*, Werner Muller§, Norbert Wagner§, and Lynn Puddington*

From the * Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington, Connecticut 06037; the {ddagger} 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 {alpha}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-{alpha}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 {alpha}Eβ7 integrin appeared to play no role in migration during a primary CD8 T cell immune response in vivo. Furthermore, despite dramatic upregulation of {alpha}Eβ7 by CD8 T cells after entry into the epithelium, long-term retention of intestinal intraepithelial lymphocytes was also {alpha}Eβ7 independent.

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

Address correspondence to Leo Lefrançois, UCONN Health Center, MC1310, Department of Medicine, 263 Farmington Ave., Farmington, CT 06030. Phone: 860-679-3242; Fax: 860-679-1287; E-mail: llefranc{at}panda.uchc.edu

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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