The Distribution of MHC Class I and II Antigens on Bronchial Epithelium

Abstract

The distribution and degree of expression of Class I and Class II major histocompatibility (MHC) antigens on human lower respiratory tract epithelium were evaluated in five freshly obtained pneumonectomy and lobectomy specimens using an immunoperoxidase technique. Multiple sites were examined from each specimen, and two independent observers graded each sample as positive, equivocal, or negative compared with control slides. Interobserver agreement was high. From a total of 120 grade determinations, 114 showed complete concordance and only one showed a positive/negative discordance. Both Class I (HLA-A,B,C) and Class II (HLA-DR) antigens were uniformly and strongly expressed throughout the major, lobar, and segmental bronchi of each sample, the bronchiolar epithelium, and the alveolar epithelium. Paired samples of adjacent lower respiratory tract epithelium harvested with the fiberoptic bronchoscope and during pathologic examination, respectively, revealed an identical staining pattern for these antigens. Staining for HLA-DQ expression (a subset of MHC Class II antigens) was generally weaker and appeared more variable, with four negative, six equivocal, and 30 positive samples. Our observations demonstrate the widespread expression of Class I antigens on airway epithelium and reveal for the first time the ubiquitous nature of Class II MHC antigen (HLA-DR) expression throughout the lower respiratory tract. Furthermore, they attest to the adequacy of bronchoscopically obtained samples for immunologic staining. These results provide a basis for both a putative mechanism of bronchocentric rejection phenomena after human heart-lung transplantation and for the means to monitor it prospectively.

Intranasal Exposure to Bacterial Superantigens Induces Airway Inflammation in HLA Class II Transgenic Mice

“…There is abundant expression of MHC class II molecules within the airways and alveoli (18). There are professional as well as nonprofessional antigen-presenting cells present in airways and lungs (18,19,29,53,99). The airways are also lined with the bronchus-associated lymphatic (21,72).…”

Interferon gamma and interleukin 4 stimulate prolonged expression of inducible nitric oxide synthase in human airway epithelium through synthesis of soluble mediators.

“…Further evidence of the presence and activity of these cytokines in the epithelial lining fluid is provided by studies which demonstrate expression of IFN␥-and IL-4-inducible genes in the human airway epithelium in vivo. Specifically, intercellular adhesion molecule-1 and HLA-DR, which are selectively induced by IFN␥ in HAEC in culture (50,51), are both continuously expressed by normal human airway epithelial cells in vivo (52)(53)(54). Interestingly, while human airway epithelial cells have Ͼ 80% positivity for MHC class I (HLA-A, B, and C) and II (HLA-DR) expression in vivo, similar to iNOS, the HLA-DR expression is lost when cells are removed from the lung environment.…”

Eotaxin protein and gene expression in guinea-pig lungs: constitutive expression and upregulation after allergen challenge

“…In respect of the eotaxin protein identified in the alveolar macrophages, the combination of the tenfold increase of macrophages after allergen challenge and the threefold increase in the percentage of eotaxin-positive cells results in a 30 fold increase of eotaxin-positive macrophages in the alveolar region compared with the naive animals. Macrophages as well as epithelial cells are ideally placed to sample allergen in inspired air and both are capable of expressing cell surface human leucocyte antigen-DR (HLA-DR) [34][35][36] and of responding in an antigen-specific fashion. Interestingly, the increase of eotaxin in macrophages showed a strong association with its upregulation in large airway epithelium (rcorr=0.95; p<0.0001) indicating a co-ordinated allergic response throughout the respiratory tract.…”