The inflammation within the lower respiratory tract of individuals with pulmonary sarcoidosis is dominated by large numbers of helper T lymphocytes that proliferate and spontaneously release interleukin 2 (IL-2). To identify the lymphocyte subpopulation that releases IL-2 in this disorder, lung lymphocytes recovered by bronchoalveolar lavage were characterized using the monoclonal antibodies Leu4 (T lymphocyte), Leu 3 (helper/inducer), Leu 2 (suppressor/cytotoxic), and anti-HLA-DR, and separated by panning and flow cytometry. The majority of the IL-2 spontaneously released by T cells in the sarcoid lung was contributed by the Leu3+ cell population (Leu3+ 65 ± 23 IL-2 units released/106 cells per 24 h; Leu2+ 9 ± 8, P<0.04). Further characterization of the lung Leu3+ T cells in sarcoid demonstrated that 30 ± 3% were expressing HLA-DR molecules on their surface compared with 6 ± 1% in normals (P<0.01). Importantly, the subpopulation of Leu3+ lung T lymphocytes expressing a high intensity of HLA-DR molecules on their surface was responsible for the majority of the release of IL-2 in the sarcoid lung (Leu3+ high-intensity DR 42 ± 17 U/106 cells per 24 h, Leu3+ low-intensity DR 8 ± 1 U/106 cells per 24 h; P<0.01). Thus, the spontaneous release of IL-2 in the lung of sarcoid patients appears to be localized to a subset of Leu3+ high-intensity DR ('activated' lung helper/inducer) T lymphocytes. Because the sarcoid lung is characterized by markedly increased numbers of these cells, it is likely that this compartmentalized T cell population plays a major role in sustaining the exaggerated localized immune processes of this disorder.
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