Pulmonary sarcoidosis is a chronic disorder characterized by heightened cellular immune processes which are localized to sites of disease (i.e. lung). We have shown in patients with active pulmonary disease that: 1) T-lymphocytes (primarily helper T-cells) are increased in lung and decreased in blood compared to controls; 2) lung T-cells spontaneously release lymphokines (mediators critical for granuloma formation) and polyclonally activate B-cells to differentiate into immunoglobulin (Ig) secreting cells; blood T-cells from these same patients and lung and blood T-cells from normals and sarcoidosis patients with inactive disease do not exhibit these characteristics. Consistent with these observations, there are increased numbers of Ig-secreting cells in lung but not blood of these patients. These observations demonstrate that evaluation of the immune system in lungs of patients with pulmonary sarcoidosis provides an opportunity to study the characteristics of the cellular immune processes which are present at sites of disease. This information cannot be obtained solely from studies of peripheral blood. In this proposal we will extend our prior observations in patients with sarcoidosis by evaluating various local immune processes which might explain, in part; a) local activation of T-cells, b) marked local increase in numbers of T-cells, c) increased local production of immunoglobulin, d) presence of activated macrophages, and e) effects of corticosteroid therapy. These studies should provide some insights into the cellular immune processes which are associated with granuloma formation in sarcoidosis.
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