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

Smyth, LJC, Kirby, JA and Cunningham, AC 2007, 'Role of the mucosal integrin αE(CD103)β7 in tissue-restricted cytotoxicity' , Clinical & Experimental Immunology, 149 (1) , pp. 162-170.

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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.

Item Type: Article
Themes: Subjects / Themes > Q Science > QR Microbiology
Subjects outside of the University Themes
Schools: Colleges and Schools > College of Science & Technology
Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences
Journal or Publication Title: Clinical & Experimental Immunology
Publisher: Wiley-Blackwell
Refereed: Yes
ISSN: 00099104
Depositing User: Users 29196 not found.
Date Deposited: 23 Dec 2010 14:14
Last Modified: 20 Aug 2013 17:44
URI: http://usir.salford.ac.uk/id/eprint/12686

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