Spontaneous release of interleukin 2 by lung T lymphocytes in active pulmonary sarcoidosis is primarily from the Leu3+DR+ T cell subset.
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), Leu3 (helper/inducer), Leu2 (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/10(6) cells per 24 h; Leu2+ 9 +/- 8, P less than 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 less than 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/10(6) cells per 24 h, Leu3+ low-intensity DR 8 +/- 1 U/10(6) cells per 24 h; P less than 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.
D000328:Adult; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008168:Lung / Q000166:cytology*; D008171:Lung Diseases / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D012137:Respiratory System / Q000166:cytology; D012507:Sarcoidosis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2