Cellular-immune responses are initiated when helper T lymphocytes respond to antigens presented in association with MHC class II region products (HLA-D region antigens) on the surface of antigen-presenting cells. It has been proposed that the increases in lymphocytes in the lungs of patients with pulmonary sarcoidosis and the enhanced antigen-presenting function of alveolar macrophages obtained by bronchoalveolar lavage might relate to increased expression of HLA-D region antigens on the alveolar macrophages of these patients. Most studies have been limited to measuring only the percentages of alveolar macrophages expressing HLA-DR antigens using standard immunofluorescent or im- munocytochemical staining methods. These studies, with only one exception, have concluded that the majority of alveolar macrophages express HLA-DR antigens and that no differences in percentages occur between patients with sarcoidosis and normal volunteers. This led Campbell et al to explore whether the density of expression of HLA-DR on alveolar macrophages might be increased in patients with sarcoidosis compared with control subjects. They used a technique employing scanning and integrating microden- sitometry and a monoclonal antibody conjugated to glucose oxidase to quantify the density of HLA-DR; they concluded that expression was significantly increased on alveolar macrophages in pulmonary sarcoidosis. They suggested that this increase might be associated with the increases in T lymphocytes in the lavage samples of these patients, but they have neither tested this possibility nor explored the relevance to clinical features. By contrast, Maron et al have recently reported in a brief abstract that expression of HLA-DR on alveolar macrophages from patients with the nongranulomatous fibrosing lung disease idiopathic pulmonary fibrosis (synonym: cryptogenic fibrosing alveolitis [CFA]) is reduced compared with that of healthy volunteers.
The aim of our study was to confirm these preliminary reports by using flow cytometric techniques to objectively measure the intensity of expression of HLA-D region products on alveolar macrophages, as well as the percentages of positive and negative cells. We have also extended the earlier work by exploring not only HLA-DR but also HLA-DQ and DP on alveolar macrophages since there is now evidence that HLA-DQ and DP expression may be a feature of the most efficient antigen presenting in the blood. In addition, we have studied expression of transferrin receptors by alveolar macrophages as another potential phenotypic marker of cell activation. We have investigated patients with extrinsic allergic alveolitis (EAA) as well as those with pulmonary sarcoidosis, since both are granulomatous lung diseases associated with increased lymphocytes in lung lavage samples, and have compared the findings with those in patients with nongranulomatous fibrosing lung diseases, in particular CFA and fibrosing alveolitis (FA) associated with scleroderma where increases in granulocytes are more common in lavage. Finally, we have explored whether the levels of HLA-D region antigens on alveolar macrophages from patients with sarcoidosis and EAA show any correlation with the levels or subpopulations of lavage lymphocytes in these patients or with their lung function measurements. Viagra Super Active