LOCALIZATION OF THE IMMUNE-RESPONSE IN SARCOIDOSIS

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Abstract
Pulmonary sarcoidosis is an interstitial disease characterized by granulomas within the lung parenchyma, anergy to a variety of skin tests and decreased numbers of circulating T[thymus-derived]-lymphocytes. To evaluate the effector cell populations present at sites of disease in patients with active pulmonary sarcoidosis, inflammatory and immune effector cells were isolated from lung via bronchoalveolar lavage and compared to comparable cell populations from the peripheral blood of the same patients and similar cell populations of normal subjects and patients with idiopathic pulmonary fibrosis. Patients with sarcoidosis had a marked increase in the percentage of T lymphocytes in the lung despite a significant peripheral blood T lymphocytopenia. Many of these T lymphocytes demonstrated surface marker characteristics associated with lymphocyte activation, and they spontaneously secreted leukocyte inhibitory factor. In contrast to patients with sarcoidosis, normal subjects and patients with idiopathic pulmonary fibrosis had similar percentages of T lymphocytes in lung and blood, and there was no evidence for T lymphocyte activation. Analysis of lymphocytes in uninvolved marrow from 7 of 8 patients with sarcoidosis revealed proportions of T lymphocytes similar to those in the marrows of normal subjects and patients with idiopathic pulmonary fibrosis. In comparison, 1 patient with sarcoidosis had large numbers of T lymphocytes in bone marrow, but only in areas where there were granulomas in the marrow. The alveolitis of pulmonary sarcoidosis is characterized by large numbers of activated T lymphocytes, and there is an anatomic localization of the immune response in sarcoidosis in that analysis of uninvolved tissues such as peripheral blood may not reflect local immune responses at sites of granuloma formation.