T-CELL RECEPTOR REPERTOIRE OF T-LYMPHOCYTES RECOVERED FROM THE LUNG AND BLOOD OF PATIENTS WITH SARCOIDOSIS

We evaluated the repertoire of V beta segments used in forming the T-c ell receptor of lavage and blood T lymphocytes from 11 sarcoid patient s and 10 normal subjects using procedures based on quantitative polyme rase chain reaction, permitting analysis of both the abundance of tran scripts using each of 20 different V beta families and the diversity o f the VDJC beta rearrangements within each V beta family. Blood and lu ng T cells from sarcoid patients had a very diverse V beta repertoire. For all V beta families but one, the abundance of the V beta transcri pts fell within the mean +/- 2 SD of that observed for normal blood ly mphocytes; no difference in the overall abundance was observed compari ng lavage and blood T cells, and the length of VDJC beta rearrangement s for a given V beta family in samples from sarcoid patients was usual ly quite heterogeneous. Despite the overall polyclonality, evidence fo r selective expansion of T cells was found, in that an increased abund ance of V beta 19 transcripts was observed for sarcoid blood and/or lu ng T cells in eight out of 11 patients studied, and rearrangements of a single predominant length using certain (e.g., V beta 19, V beta 14) , but not all, V beta families were present. Sequencing confirmed the presence of a single predominant VDJC beta rearrangement in these case s. These findings suggest that the alveolitis in sarcoidosis results f rom two distinct processes, a local clonal expansion of T cells associ ated with an apparently nonspecific accumulation of T cells with an ex tremely diverse V beta repertoire.