Role of integrin alpha(E)(CD103)beta(7) for tissue-specific epidermal localization of CD8(+) T lymphocytes

Tissue-specific T cell localization is crucial for immune surveillance of n ormal 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 g uiding this spatial compartmentalization are not completely understood, how ever. Here, we demonstrate that 55% (+/-9.7%, n = 14) of the epidermal T ce lls, 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 a lpha (E)(CD103)beta (+)(7). Integrin alpha (E)(CD103)beta (7) was not detec ted in normal skin (n = 10), and less than 1% of peripheral blood lymphocyt es derived from normal (n = 11) or psoriatic (it = 10) donors expressed alp ha (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 o n 6.1% (+/-2.3%) of CD4(+) cells, suggesting selective inducibility on CD8( +) lymphocytes. Whereas similar overall expression of transforming-growth-f actor-beta1(-)specific mRNA was detected in normal and psoriatic skin by re al-time quantitative polymerase chain reaction, immunohistochemistry reveal ed focal overexpression of transforming growth factor beta (1) underneath p soriatic, 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 bloc ked 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) a ppears to contribute to tissue-specific epidermal localization of CD8(+) T lymphocytes.