Pulmonary Sarcoidosis and T-cell Receptor Genes Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that involves the lungs in over 90% of individuals, Sarcoidosis results in considerable morbidity, particularly with respect to the lungs, eyes, skin, heart and nervous system. Treatment with corticosteroids may be toxic and ineffective. As many as 5% of individuals with pulmonary sarcoidosis die of causes directly related to the disease. With an approximate incidence in the U.S. of 11-40 per 100,000 people, sarcoidosis represents a significant health problem. T-cells are involved in the pathogenesis of the disease since """"""""activated"""""""", lymphokine-releasing CD4+ T-helper cells accumulate at sites of disease. T-cells expressing specific T-cell antigen receptor (TCR) gene products preferentially with sarcoid. These observations lead to the hypothesis that sarcoidosis is the result of a specific T-cell immune response to exogenous or self-antigens. These studies will test these hypothesis by determining whether T-cells with restricted T-cell receptor diversity accumulate in the epithelial lining fluid and/or blood of individuals with active pulmonary sarcoidosis. They will determine if T-cells expressing distinct T-cell receptor gene elements are found in affected sarcoid tissue and whether they have characteristics of activated T-cells. These studies will also examine whether these observations are specific for sarcoidosis by evaluating whether T-cells with limited T-cell receptor diversity are found in the lower respiratory tract or blood of individuals with pulmonary tuberculosis or normal individuals. To gain insights into the nature of the stimulus that results in the accumulation of T-cells with distinct TCR in sarcoidosis, a molecular characterization of the T-cell receptor genes of these T-cells will be performed and compared to TCR of T-cells of normal individuals and individuals with pulmonary tuberculosis. Furthermore, the role these T-cells play in the pathogenesis of sarcoidosis will be investigated by isolating and expanding these T-cells in culture in order to study their specificity, their ability to release lymphokines, and methods to specifically suppress their activity.
