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

Smyth, LJC; Kirby, JA; Cunningham, AC

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.

Citation

Smyth, L., Kirby, J., & Cunningham, A. (2007). Role of the mucosal integrin αE(CD103)β7 in tissue-restricted cytotoxicity. https://doi.org/10.1111/j.1365-2249.2007.03385.x

• Journal Article Type: Article
• Publication Date: Jan 1, 2007
• Deposit Date: Dec 23, 2010
• Journal: Clinical & Experimental Immunology
• Print ISSN: 00099104
• Peer Reviewed: Peer Reviewed
• Volume: 149
• Issue: 1
• Pages: 162-170
• DOI: https://doi.org/10.1111/j.1365-2249.2007.03385.x
• Publisher URL: http://dx.doi.org/10.1111/j.1365-2249.2007.03385.x