Selective activation and accumulation of oligoclonal Vβ-specific T cells in active pulmonary sarcoidosis

Abstract

Sarcoidosis is a granulomatous disease in which activated T cells, responding to an unidentified stimulus, accumulate at sites of disease such as the lung. To evaluate the hypothesis that active sarcoidosis is characterized by a selective activation and expansion of a limited repertoire of T cell receptor (TCR) specific T cells, we analyzed TCR Vβ gene expression in lung and blood T cells of patients with active sarcoidosis and, for comparison, normal individuals using polymerase chain reaction amplification of 20 Vβ gene families. Analysis of normal bronchoalveolar lavage T cells revealed TCR Vβ distributions similar to that of normal blood, providing evidence for a lack of generalized skewing of the T cell repertoire in the normal, noninfected lung. Compared to normal lung and blood, subgroups of individuals with sarcoidosis demonstrated biased expression of one or more Vβ genes in either the lung or blood. Five Vβ gene families (Vβ5, Vβ8, Vβ15, Vβ16, and Vβ18) were most frequently utilized in a biased fashion by sarcoid lung or blood T cells. Furthermore, dramatic skewing of the T cell repertoire was apparent when sarcoid lung and blood T cells were expanded by short-term culture with IL-2. Sequence analysis demonstrated a bias in Vβ gene expression was usually due to expansion of select Vβ-specific clones, some of which contained a similar V(D)J junctional region motif. These observations provide evidence for a selective activation and accumulation of antigen-specific Vβ-expressing T cells in sarcoidosis.