Expression of HLA Class II Genes in Alveolar Macrophages of Patients with Sarcoidosis

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Abstract
Sarcoidosis is characterized by the accumulation of activated helper/inducer T-cells and macrophages at sites of disease. The accumulation of these T-cells may be related to the ability of sarcoid alveolar macrophages to present antigen and stimulate lymphocyte proliferation in an exaggerated fashion. In the context that HLA Class II gene (HLA-DR, DQ, and DP) expression is essential to the interaction of lymphocytes with antigen-presenting cells such as macrophages, we have evaluated the hypothesis that the expression of Class II genes may be up-regulated in sarcoid alveolar macrophages. Northern blot and dot blot analysis with 32P-labeled cDNA probes for HLA-DR, DQ, and DP genes revealed that both normal and sarcoid alveolar macrophages contain Class II mRNA transcripts, but that the levels in sarcoid and normal alveolar macrophages are similar (p > 0.3, all comparisons). Furthermore, evaluation of surface expression of Class II molecules with monoclonal antibodies and flow cytometry analysis demonstrated tht alveolar macrophages of both patients with sarcoidosis and normal subjects express all three Class II molecules, DR, DQ, and DP, but there were no significant differences between sarcoid patients and normal subjects in the proportions of macrophages expressing these surface molecules. However, there was a significantly higher surface density of Class II molecules on sarcoid alveolar macrophages (p < 0.05, all comparisons sarcoid to normal). Thus, enhanced surface expression of Class II molecules is observed on sarcoid alveolar macrophages, consistent with the concept that the expression of Class II molecules may play an important role in the ability of sarcoid alveolar macrophages to present antigen and stimulate lymphocytes, explaining in part the accumulation of activated helper T-cells in sarcoidosis.