PREFERENTIAL USAGE OF THE T-CELL ANTIGEN RECEPTOR BETA-CHAIN CONSTANT REGION C-BETA-1 ELEMENT BY LUNG LYMPHOCYTES-T OF PATIENTS WITH PULMONARY SARCOIDOSIS

Evaluation of the T-cells accumulating at sites of disease in active sarcoidosis suggests the accumulation process is not random, evidenced by a bias in the types of T-cells present. To evaluate the concept that this bias extends to the accumulation of T-cells with the preferential use of specific T-cell antigen receptor (TCR) beta-chain constant region elements, beta-chain mRNA transcripts of lung and blood T-cells of normal subjects and patients with pulmonary sarcoldosis were compared for the relative usage of constant region beta-1 or beta-2 elements. Quantitative evaluation of C-beta-1 and C-beta-2 mRNA transcripts demonstrated a C-beta/C-beta-2 usage in normal blood of 0.63 +/- 0.02, similar to that of normal lung (0.64 +/- 0.06, p > 0.7), and in sarcoid blood (0.59 +/- 0.03, p > 0.2). In contrast, the lung T-lymphocytes of patients with sarcoldosis reflected a marked bias in the usage of C-beta-1 elements (C-beta-1/C-beta-2: 0.88 +/- 0.06, p < 0.001 compared with sarcoid blood and normal blood; p < 0.02 compared with normal lung). Interestingly, a subgroup of these patients (six of 18) showed a markedly exaggerated skewing in the use of C-beta-1 elements (C-beta-1/C-beta-2 ratio > 1, i.e., > 3 standard deviations above mean), demonstrating heterogeneity among sarcoid patients with regard to specific C-beta-1 usage. These observations provide further evidence that there is a bias in the type of T-lymphocytes that accumulate in affected organs in sarcoidosis, and they are consistent with the concept that there is selection for T-lymphocytes with specific T-cell antigen receptors in association with sarcoid inflammation.