Role of Integrin αE(CD103)β7 for Tissue-Specific Epidermal Localization of CD8+ T Lymphocytes

Tissue-specific T cell localization is crucial for immune surveillance of normal tissues and the pathogenesis of inflammatory disorders. In psoriatic skin, CD8+ lymphocytes predominantly reside within the epidermis, whereas CD4+ T cells are most abundant within the dermis. Molecular mechanisms guiding this spatial compartmentalization are not completely understood, however. Here, we demonstrate that 55% (±9.7%, n = 14) of the epidermal T cells, predominantly of the CD8+ phenotype, expressed the integrin αE(CD103)β7. In contrast, only 5% (±2.0%) of the dermal T cells were αE(CD103)β7+. Integrin αE(CD103)β7 was not detected in normal skin (n = 10), and less than 1% of peripheral blood lymphocytes derived from normal (n = 11) or psoriatic (n = 10) donors expressed αE(CD103). When cultured T lymphoblasts (n = 12 donors) were stimulated with transforming growth factor β1, expression of integrin αE(CD103)β7 was induced on 52.8% (±16.2%) of CD8+ cells, but only on 6.1% (±2.3%) of CD4+ cells, suggesting selective inducibility on CD8+ lymphocytes. Whereas similar overall expression of transforming-growth-factor-β1-specific mRNA was detected in normal and psoriatic skin by real-time quantitative polymerase chain reaction, immunohistochemistry revealed focal overexpression of transforming growth factor β1 underneath psoriatic, but not normal, epidermis. This heterogenous transforming growth factor β1 expression may contribute to induction of αE(CD103) in vivo. Adhesion of transforming-growth-factor-β1-stimulated CD8+, but not CD4+, T cells to cultured keratinocytes and psoriatic epidermis in frozen sections could be significantly inhibited by antibodies that blocked the αE(CD103)/E–cadherin interaction. Co-culture of lymphoblasts and keratinocytes resulted in marginal enhancement of αE(CD103)β7 expression in some cases. Overall, integrin αE(CD103)β7 appears to contribute to tissue-specific epidermal localization of CD8+ T lymphocytes