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Role of the mucosal integrin αE(CD103)β7 in tissue-restricted cytotoxicity

Lookup NU author(s): Professor John Kirby

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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, αE(CD103)β7. 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)-β. The functional effect of CD103 expression was investigated in 51Cr-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 αEβ7- 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. © 2007 British Society for Immunology.


Publication metadata

Author(s): Smyth LJC, Kirby JA, Cunningham AC

Publication type: Article

Publication status: Published

Journal: Clinical and Experimental Immunology

Year: 2007

Volume: 149

Issue: 1

Pages: 162-170

Print publication date: 01/07/2007

ISSN (print): 0009-9104

ISSN (electronic): 1365-2249

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/j.1365-2249.2007.03385.x

DOI: 10.1111/j.1365-2249.2007.03385.x

PubMed id: 17403056


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