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  • Title: Role of the mucosal integrin alpha(E)(CD103)beta(7) in tissue-restricted cytotoxicity.
    Author: Smyth LJ, Kirby JA, Cunningham AC.
    Journal: Clin Exp Immunol; 2007 Jul; 149(1):162-70. PubMed ID: 17403056.
    Abstract:
    The effectiveness of lung transplantation is marred by the relatively high incidence of rejection. The lung normally contains a large population of lymphocytes in contact with the airway epithelium, a proportion of which expresses the mucosal integrin, alpha(E)(CD103)beta(7). This integrin is not a homing receptor, but is thought to retain lymphocytes at the epithelial surface. Following transplantation, a population of 'tissue-restricted' cytotoxic T cells (CTL) have been identified which have the ability to lyse epithelial cells, but not major histocompatibility complex (MHC)-identical splenic cells. We tested the hypothesis that expression of the mucosal integrin confers the ability of CTL to target and destroy e-cadherin expressing targets. Immunohistochemical and flow cytometric analyses were used to demonstrate the relevance of this model to human lung. Allo-activated CTL were generated in mixed leucocyte reactions and CD103 expression up-regulated by the addition of transforming growth factor (TGF)-beta. The functional effect of CD103 expression was investigated in (51)Cr-release assays using e-cadherin-expressing transfectant targets. Human lung epithelial cells express e-cadherin and one-third of intraepithelial lymphocytes (IEL) expressed CD103. Allo-activated and bronchoalveolar lavage (BAL) lymphocytes express more CD103 than those in blood. Transfection of e-cadherin into murine fibroblasts conferred susceptibility to lysis by alpha(E)beta(7)-expressing CTL which could be blocked by specific monoclonal antibodies to CD103 and e-cadherin. CD103 functions to conjugate CTL effectors to e-cadherin-expressing targets and thereby facilitates cellular cytotoxicity. E-cadherin is expressed prominently by epithelial cells in the lung, enabling CTL to target them for destruction.
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