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

2001; Elsevier BV; Volume: 117; Issue: 3 Linguagem: Inglês

10.1046/j.0022-202x.2001.01481.x

1523-1747

K. Pauls, Margarete Schön, Robert Kubitza, Bernhard Homey, Andrea Wiesenborn, Percy Lehmann, Thomas Ruzicka, Christina M. Parker, Michael P. Schön,

Immunotherapy and Immune Responses

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