Accessory cell function of airway epithelial cells

Abstract

Oei, Erwin, Thomas Kalb, Prarthana Beuria, Matthieu Allez, Atsushi Nakazawa, Miyuki Azuma, Michael Timony, Zanetta Stuart, Houchu Chen, and Kirk Sperber. Accessory cell function of airway epithelial cells.We previously demonstrated that airway epithelial cells (AECs) have many features of accessory cells, including expression of class II molecules CD80 and CD86 and functional Fcγ receptors. We have extended these studies to show that freshly isolated AECs have mRNA for cathepsins S, V, and H [proteases important in antigen (Ag) presentation], invariant chain, human leukocyte antigen (HLA)-DM-α and HLA-DM-β, and CLIP, an invariant chain breakdown product. A physiologically relevant Ag, ragweed, was colocalized with HLA-DR in AECs, and its uptake was increased by granulocyte-macrophage colony-stimulating factor and IFN-γ treatments, which had no effect on CD80 and CD86 expression. We demonstrate the presence of other costimulatory molecules, including B7h and B7-H1, on AECs and the increased expression of B7-H1 on AECs after treatment with granulocyte-macrophage colony-stimulating factor and IFN-γ. Finally, we compared T cell proliferation after allostimulation with AECs and dendritic cells (DCs). The precursor frequency of peripheral blood T cells responding to AECs was 0.264% compared with 0.55% for DCs. DCs stimulated CD45RO+, CD45RA+, CCR7+and CCR7−CD4+, and CD8+T cells, whereas AECs stimulated only CD45RO+, CD45RA−, CCR7−, CD4+, and CD8+T cells. There was no difference in cytokine production, type of memory T cells stimulated (effector vs. long-term memory), or apoptosis by T cells cocultured with AECs and DCs. The localization of AECs exposed to the external environment may make them important in the regulation of local immune responses.

Alveolar Epithelial Type II Cells Induce T Cell Tolerance to Specific Antigen

“…In contrast, a study by Cunningham et al (9), which also used isolated primary human Type II cells but included nonspecific Ab controls, found no CD80 or CD86 expressed on human Type II cells by flow cytometry. Other studies reporting the expression of CD80 and/or CD86 on Type II cells did not use primary isolates of Type II cells, but rather used the carcinoma-derived A549 cell line (30,31), which is sometimes used as a Type II-like cell line but is not truly representative of Type II cells of the alveolar space (32). Other reports used cultures of respiratory epithelial cells that may contain Type II cells, but also likely includes other epithelial cells that may confound their results (31).…”

“…Other studies reporting the expression of CD80 and/or CD86 on Type II cells did not use primary isolates of Type II cells, but rather used the carcinoma-derived A549 cell line (30,31), which is sometimes used as a Type II-like cell line but is not truly representative of Type II cells of the alveolar space (32). Other reports used cultures of respiratory epithelial cells that may contain Type II cells, but also likely includes other epithelial cells that may confound their results (31). Thus, it is important to consider these issues when comparing our studies with those referenced above.…”

miR-31 Dysregulation in Cystic Fibrosis Airways Contributes to Increased Pulmonary Cathepsin S Production

“…predominant expression in antigenpresenting cells; however, more recent work has demonstrated expression of CTSS in airway epithelial cells (24,25,32). Given the prevalence of CTSS in the lungs of children with CF, we investigated whether pulmonary epithelial cells represent a possible source of CTSS in the CF lung.…”

“…A range of epithelial dysfunctions have been implicated in the pathogenesis of CF lung disease, which are ultimately consequences of mutations in the CF transmembrane conductance regulator (CFTR) gene. Given that epithelial cells have been reported to express CTSS (21,24,25), we investigated the hypothesis that CF airway epithelial cells contribute to the protease burden of the CF lung by releasing increased levels of CTSS compared with non-CF control cells, and explore the mechanism responsible for our observations. Some of the results of these studies have been previously reported in the form of abstracts (26,27).…”

Role of cathepsin S in ozone-induced airway hyperresponsiveness and inflammation

“…Therefore, its localisation in the lung may pinpoint to an important function for cathepsin S. Thus, cathepsin S is also expressed in antigen-presenting cells (APC), such as macrophages and dendritic cells, and in MHC Class II cells, and could mediate CD4 + T-cell mediated immune responses. In addition, it is expressed in non-professional APCs, such as epithelial cells (12)(13)(14). Such distribution strongly suggests a role for cathepsin S in immune and inflammatory processes such that provoked by ozone exposure.…”