Preferential Usage of the T-Cell Antigen Receptor β-Chain Constant Region Cβ1 Element by Lung T-Lymphocytes 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 sarcoidosis 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 1/C beta 2 usage in normal blood of 0.63 +/- 0.02, similar to that of normal lung (0.64 +/- 0.06, p greater than 0.7), and in sarcoid blood (0.59 +/- 0.03, p greater than 0.2). In contrast, the lung T-lymphocytes of patients with sarcoidosis reflected a marked bias in the usage of C beta 1 elements (C beta 1/C beta 2: 0.88 +/- 0.06, p less than 0.001 compared with sarcoid blood and normal blood; p less than 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 greater than 1, i.e., greater than 3 standard deviations above mean), demonstrating heterogeneity among sarcoid patients with regard to specific C beta 1 usage.(ABSTRACT TRUNCATED AT 250 WORDS)