ANALYSIS OF T-CELL SUBSETS AND BETA-CHEMOKINES IN PATIENTS WITH PULMONARY SARCOIDOSIS

Background - Sarcoidosis is a systemic granulomatous disorder of unkno wn origin characterised by accumulation of T lymphocytes and macrophag es in multiple organs. Several cytokines and adhesion molecules may co ntribute to the accumulation of T lymphocytes in pulmonary sarcoidosis . The distribution of T lymphocyte subsets, T cell bearing CD11a and b eta chemokines such as regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory peptide 1 alpha (MIP-1 alph a), and macrophage chemoattractant protein 1 (MCP-1) in bronchoalveola r lavage (BAL) fluid and peripheral blood were compared in untreated p atients with sarcoidosis and normal subjects. Methods - Flow cytometri c analysis with monoclonal antibodies to cell surface antigens was use d to identify T lymphocyte subsets in the BAL fluid of untreated patie nts with sarcoidosis (n=40) - either without (group A, n=12) or with ( group B, n = 28) radiological evidence of pulmonary involvement - and in 22 normal subjects. The level of different beta chemokines was esti mated by enzyme linked immunosorbent assay (ELISA). Results - A high p ercentage of CD3+ cells, CD4+- cells expressing HLA-DR antigen, and a high CD4/CD8 ratio were detected in the BAL fluid of patients compared with normal subjects. In particular, CD4+ CD29+ memory T cells were s ignificantly increased in patients with sarcoidosis. Furthermore, thes e cells were higher in those in group B than group A. The level of RAN TES in the BAL fluid of patients was significantly higher than in norm al subjects and correlated well with the percentage, number, and expre ssion of CD29 on CD4 cells. The expression of CD11a (alpha chain of ly mphocyte function associated antigen-1, LFA-1) on CD3+ cells in the BA L fluid of patients with sarcoidosis was not different from that of no rmal subjects. However, the expression of CD11a on CD3+ cells in the B AL fluid of patients in group A was significantly lower than that of p atients in group B and normal subjects. Conclusions - These results su ggest a possible interaction between activated memory T cells bearing CD11a and RANTES which may contribute to the pulmonary involvement in patients with sarcoidosis.