Bias toward use of a specific T cell receptor β-chain variable region in a subgroup of individuals with sarcoidosis

Abstract

To evaluate the concept that biases in the usage of T cell antigen receptor β variable (V) regions may be manifested in T lymphocytes that accumulate in nonmalignant, T cell-mediated human disorders, a V(β)8-specific antibody (anti-T(i3A), 5REX9H5) was used to evaluate lung and blood T cells in pulmonary sarcoidosis, a chronic granulomatous disorder of unknown etiology. Whereas normal patients had <5% T(i3A+) lung (n = 7) and/or blood (n = 9) lymphocytes, strikingly, a subgroup (8 of 21) with active pulmonary sarcoidosis had >7% T(i3A+) lung and/or blood T cells and a higher proportion of T(i3A+) lymphocytes in the lung compared with blood. Dual-color flow cytometry demonstrated compartmentalization of T(i3A+) CD4+ lymphocytes to lung and T(i3A+) CD8+ lymphocytes to blood. Analysis with a 32P-labeled V(β)8 probe revealed that sarcoid lung T lymphocytes contained higher amounts of V(β)8+ mRNA than autologous blood T cells. However, Southern analysis of sarcoid lung and blood T cell DNA demonstrated no evidence of clonal rearrangements of V(β)8 genes. These observations demonstrate a clear bias toward the use of at least one V(β) region in sarcoidosis, and suggests T cells accumulate secondary to external selective pressure, rather than in a random polyclonal fashion or by clonal expansion of one or few T cell clones.