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 alpha (E)(CD103)beta (7). In contrast, only 5% (+/-2.0%) of the dermal T cells were alpha (E)(CD103)beta (+)(7). Integrin alpha (E)(CD103)beta (7) was not detected in normal skin (n = 10), and less than 1% of peripheral blood lymphocytes derived from normal (n = 11) or psoriatic (it = 10) donors expressed alpha (E)(CD103). When cultured T lymphoblasts (n = 12 donors) were stimulated with transforming growth factor beta (1), expression of integrin alpha (E)(CD103)beta (7) 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-beta1(-)specific mRNA was detected in normal and psoriatic skin by real-time quantitative polymerase chain reaction, immunohistochemistry revealed focal overexpression of transforming growth factor beta (1) underneath psoriatic, but not normal, epidermis. This heterogenous transforming growth factor beta (1) expression may contribute to induction of alpha (E)(CD103) in vivo. Adhesion of transforming-growth-factor-beta (1)-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 alpha (E)(CD103)/E-cadherin interaction. Co-culture of lymphoblasts and keratinocytes resulted in marginal enhancement of alpha (E)(CD103)beta (7) expression in some cases. Overall, integrin alpha (E)(CD103)beta (7) appears to contribute to tissue-specific epidermal localization of CD8(+) T lymphocytes.