CD8 and CD103 Are Highly Expressed in Asthmatic Bronchial Intraepithelial Lymphocytes

Abstract

Background: Although characteristics of intraepithelial lymphocytes (IELs) in mucosal immunity have been well defined in the intestine, bronchial IELs have been little investigated. Recently, we showed that bronchial IELs have a distinct function that partly resembles that of intestinal IELs; however, surface antigen expression of bronchial IELs and the relationship of that expression to airway disease have not been studied. Methods: We analyzed phenotypic profiles of human bronchial IELs and lamina propria lymphocytes (LPLs) by double-staining immunohistochemistry using full-thickness bronchial specimens (10 nonasthmatic controls and 7 asthmatics) from lung resections. Results: In controls, the percentage of CD4+ cells was lower, and the percentage of CD8+ cells was higher in IELs compared to LPLs (CD4: median 50.0% in IELs vs. 65.9% in LPLs, p = 0.01; CD8: 50.9% in IELs vs. 34.4% in LPLs, p = 0.007). The percentage of cells positive for CD103 (αE-integrin) was higher in IELs than that in LPLs (median 60.1% in IELs vs. 16.9% in LPLs; p < 0.001). In IELs from asthmatics, these characteristics were particularly significant (CD4: median 26.2%, p = 0.008; CD8: 79.8%, p = 0.007; CD103: 76.2%, p = 0.019; all compared with IELs from nonasthmatics). Conclusions: These results suggest that human bronchial IELs have roles distinct from subsets of other lymphocytes, and that CD8+ cells and CD103+ cells have potentially important functions in the bronchial epithelium.

CD8+ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung

“…However, our findings in this group are comparable to data published by Hirosako et al, who have meticulously analyzed CD103 + expression by intraepithelial T cells in human bronchi (third to fifth generation) in a patient group that is demographically very similar to our cohort (14,16). They showed that a range of 74% to 94% of intraepithelial CD8 + cells expressed CD103, whereas only 8% to 25% of lamina propria T cells expressed CD103.…”

“…Immunohistochemistry confirmed that most lung CD103 + CD3 + CD8 + T cells were indeed located intraepithelially above the basement membrane of the small airways ( Figure 1C), as was previously published (13)(14)(15)(16).…”

“…Intraepithelial CD8 + T cells express αEβ7 integrin, which binds to epithelial cadherin (E-cadherin), expressed by the epithelial cells (11)(12)(13)(14)(15)(16). This interaction retains the IELs in the vicinity of the epithelium (17)(18)(19).…”

E-cadherin gene polymorphisms in asthma patients using inhaled corticosteroids

“…Previously, SONT et al [34] found that despite ICS treatment, CD8+ T-cell infiltration might persist in asthma patients and that CD8+, but not CD4+, cells are associated with BHR [34] and lung function decline [35], and recently, HIROSAKO et al [8] showed that CD8 and CD103 (ligand for E-cadherin) are highly expressed in asthmatic bronchial intraepithelial lymphocytes.…”

“…E-cadherin, the major cadherin expressed in epithelial cells, is an adhesion molecule that is able to establish and stabilise cellular junctions between adjacent cells in the presence of Ca 2+ [7] and is coded by the CDH1 gene on chromosome 16q22.1. HIROSAKO et al [8] suggested that human bronchial intraepithelial lymphocytes have roles distinct from subsets of other lymphocytes, and that CD8+ cells and CD103+ (ligand of Ecadherin) cells have potentially important functions in the bronchial epithelium.…”