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) β-chain constant region elements, β-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 β1 or β2 elements. Quantitative evaluation of Cβ1 and Cβ2 mRNA transcripts demonstrated a Cβ1/Cβ2 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 sarcoidosis reflected a marked bias in the usage of Cβ1 elements (Cβ1/Cβ2: 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 Cβ1 elements (Cβ1/Cβ2 ratio > 1, i.e., > 3 standard deviations above mean), demonstrating heterogeneity among sarcoid patients with regard to specific Cβ1 usage. These observations provide further evidence that there is a bias in the types 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.