TCR expression and clonality analysis in pulmonary sarcoidosis

Abstract

Pulmonary sarcoidosis is a granulomatous disease characterized by the accumulation of activated T cells in the lower respiratory tract. To evaluate the hypothesis that sarcoidosis is characterized by a selective activation and expansion of a limited repertoire of T cell receptor (TCR)-specific T cells, we analyzed TCRAV and TCRBV gene expression in bronchoalveolar lavage (BAL) T cells from sarcoidosis patients and, for comparison, from patients with other pulmonary diseases where lymphocyte accumulation is not observed. Increased expression of TCRAV9 and TCRAV14 in BAL T cells was observed in sarcoidosis patients compared to these controls. To ascertain whether the accumulation of AV9 and AV14 expressing BAL T cells in sarcoidosis was the result of clonal expansion, the lengths of the CDR3 regions in AV9 and AV14 transcripts were determined. Some individual patient samples showed evidence of oligoclonality. However, in most cases, the data were consistent with the presence of many different clones. These data suggest that the bulk of BAL T cells in sarcoid patients are either nonspecifically recruited or are responding to a complex mixture of antigens.