Pauls K, Schön M, Kubitza R C, Homey B, Wiesenborn A, Lehmann P, Ruzicka T, Parker C M, Schön M P
Department of Dermatology, Otto-von-Guericke University, Magdeburg, Germany.
J Invest Dermatol. 2001 Sep;117(3):569-75. doi: 10.1046/j.0022-202x.2001.01481.x.
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 alphaE(CD103)beta7. In contrast, only 5% (+/-2.0%) of the dermal T cells were alphaE(CD103)beta7+. Integrin alphaE(CD103)beta7 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 alphaE(CD103). When cultured T lymphoblasts (n = 12 donors) were stimulated with transforming growth factor beta1, expression of integrin alphaE(CD103)beta7 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 beta1 underneath psoriatic, but not normal, epidermis. This heterogenous transforming growth factor beta1 expression may contribute to induction of alphaE(CD103) in vivo. Adhesion of transforming-growth-factor-beta1-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 alphaE(CD103)/E-cadherin interaction. Co-culture of lymphoblasts and keratinocytes resulted in marginal enhancement of alphaE(CD103)beta7 expression in some cases. Overall, integrin alphaE(CD103)beta7 appears to contribute to tissue-specific epidermal localization of CD8+ T lymphocytes.
组织特异性T细胞定位对于正常组织的免疫监视和炎症性疾病的发病机制至关重要。在银屑病皮肤中，CD8 +淋巴细胞主要存在于表皮内，而CD4 + T细胞在真皮中最为丰富。然而，指导这种空间分隔的分子机制尚未完全了解。在这里，我们证明55%（±9.7%，n = 14）的表皮T细胞，主要是CD8 +表型，表达整合素αE（CD103）β7。相比之下，只有5%（±2.0%）的真皮T细胞是αE（CD103）β7 +。在正常皮肤（n = 10）中未检测到整合素αE（CD103）β7，来自正常（n = 11）或银屑病（n = 10）供体的外周血淋巴细胞中表达αE（CD103）的不到1%。当用转化生长因子β1刺激培养的T淋巴母细胞（n = 12个供体）时，整合素αE（CD103）β7在52.8%（±16.2%）的CD8 +细胞上被诱导表达，但仅在6.1%（±2.3%）的CD4 +细胞上被诱导表达，表明在CD8 +淋巴细胞上具有选择性诱导性。虽然通过实时定量聚合酶链反应在正常和银屑病皮肤中检测到转化生长因子β1特异性mRNA的总体表达相似，但免疫组织化学显示在银屑病而非正常表皮下转化生长因子β1有局灶性过表达。这种异质性的转化生长因子β1表达可能有助于体内αE（CD103）的诱导。在冷冻切片中，阻断αE（CD103）/E -钙黏蛋白相互作用的抗体可显著抑制转化生长因子β1刺激的CD8 +而非CD4 + T细胞与培养的角质形成细胞和银屑病表皮的黏附。在某些情况下，淋巴母细胞与角质形成细胞的共培养导致αE（CD103）β7表达略有增强。总体而言，整合素αE（CD103）β7似乎有助于CD8 + T淋巴细胞在组织特异性表皮中的定位。
