Alveolar macrophages that suppress T-cell responses may be crucial to the pathogenetic outcome of pulmonary sarcoidosis

The alveolar macrophage (AM) population is widely recognized to be heterogeneous; distinct subpopulations can be identified by the use of macrophage-specific monoclonal antibody (MoAb) probes. We have isolated a macrophage subset that appears to react with both MoAbs that have previously discriminated between dendritic cells and classic macrophages. In the bronchoalveolar lavage (BAL) of patients with active sarcoidosis the proportion of this specific AM subpopulation increases dramatically (30.4 +/- 4.01% compared to 6.14 +/- 1.56% in normal BAL). This AM subset not only increases in direct proportion to the lavage lymphocytosis, but also exhibits sarcoid-related differences in surface receptor expression, physiology and induction of T-cell responses. An increased number of these AM expressed a separate antigen RFD9 (which identified epithelioid cells), and had raised fibronectin content, increased phagocytosis, and high lysosomal enzyme activity. Of functional significance, we found that while in normal volunteers this specific AM subset was capable of down-regulating by as much as 40% the induction of T-cell responses set up by other stimulator macrophages, in sarcoid patients this suppressor activity was enhanced, such that T-cell responses were completely abolished. In some studies this action was masked by the reduced enhancing capacity of sarcoid inducer AM. We postulate that the presence of an increased proportion of these suppressor AM (together with their sarcoid-specific features) in active sarcoidosis is of crucial significance in determining the fate of granulomata in the lungs of these patients.

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