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The Journal of Immunology, 1999, 162: 6641-6649.
Copyright © 1999 by The American Association of Immunologists

Mucosal T Lymphocyte Numbers Are Selectively Reduced in Integrin {alpha}E (CD103)-Deficient Mice1

Michael P. Schön2,*, Anu Arya*, Elizabeth A. Murphy*, Cassandra M. Adams*, Ulrike G. Strauch*, William W. Agace*, Jan Marsal*, John P. Donohue*, Helen Her{dagger}, David R. Beier{dagger}, Sara Olson§, Leo Lefrancois§, Michael B. Brenner*, Michael J. Grusby*,{ddagger} and Christina M. Parker3,*

* Division of Rheumatology, Immunology, and Allergy, and {dagger} Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; {ddagger} Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA 02115; and § Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030

The mucosal lymphocyte integrin {alpha}E(CD103)ß7 is thought to be important for intraepithelial lymphocyte (IEL) localization or function. We cloned the murine integrin gene encoding {alpha}E, localized it to chromosome 11, and generated integrin {alpha}E-deficient mice. In {alpha}E-/- mice, intestinal and vaginal IEL numbers were reduced, consistent with the known binding of {alpha}Eß7 to E-cadherin expressed on epithelial cells. However, it was surprising that lamina propria T lymphocyte numbers were diminished, as E-cadherin is not expressed in the lamina propria. In contrast, peribronchial, intrapulmonary, Peyer’s patch, and splenic T lymphocyte numbers were not reduced in {alpha}E-deficient mice. Thus, {alpha}Eß7 was important for generating or maintaining the gut and vaginal T lymphocytes located diffusely within the epithelium or lamina propria but not for generating the gut-associated organized lymphoid tissues. Finally, the impact of {alpha}E deficiency upon intestinal IEL numbers was greater at 3–4 wk of life than in younger animals, and affected the TCR {alpha}ß+ CD8+ T cells more than the {gamma}{delta} T cells or the TCR {alpha}ß+ CD4+CD8- population. These findings suggest that {alpha}Eß7 is involved in the expansion/recruitment of TCR {alpha}ß+ CD8+ IEL following microbial colonization. Integrin {alpha}E-deficient mice will provide an important tool for studying the role of {alpha}Eß7 and of {alpha}Eß7-expressing mucosal T lymphocytes in vivo.




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