Mucosal T Lymphocyte Numbers Are Selectively Reduced in Integrin αE (CD103)-Deficient Mice

Abstract

The mucosal lymphocyte integrin αE(CD103)β7 is thought to be important for intraepithelial lymphocyte (IEL) localization or function. We cloned the murine integrin gene encoding αE, localized it to chromosome 11, and generated integrin αE-deficient mice. In αE−/− mice, intestinal and vaginal IEL numbers were reduced, consistent with the known binding of αEβ7 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 αE-deficient mice. Thus, αEβ7 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 αE deficiency upon intestinal IEL numbers was greater at 3–4 wk of life than in younger animals, and affected the TCR αβ+ CD8+ T cells more than the γδ T cells or the TCR αβ+ CD4+CD8− population. These findings suggest that αEβ7 is involved in the expansion/recruitment of TCR αβ+ CD8+ IEL following microbial colonization. Integrin αE-deficient mice will provide an important tool for studying the role of αEβ7 and of αEβ7-expressing mucosal T lymphocytes in vivo.