SELECTION OF OLIGOCLONAL V-BETA-SPECIFIC T-CELLS IN THE INTRADERMAL RESPONSE TO KVEIM-SILTZBACH REAGENT IN INDIVIDUALS WITH SARCOIDOSIS

Sarcoidosis is a multiorgan granulomatous disorder of unknown etiology characterized by noncaseating granulomas in involved tissues. A posit ive Kveim-Siltzbach reaction is a granulomatous response to an intrade rmal injection of a suspension of sarcoid tissue extract in individual s with sarcoidosis. The protracted time course and granulomatous featu res of this reaction have a striking resemblance to the Mitsuda reacti on in tuberculous leprosy, which suggests that the Kveim-Siltzbach rea ction is a response to an unknown Ag(s). To evaluate whether this reac tion is Ag-driven, an analysis of the TCR V beta repertoire in 15 Kvei m-Siltzbach reaction sites was performed using a PCR technique and pri mers specific for 20 V beta gene families. Results of this analysis de monstrated a pattern of V beta expression dominated by expression of V beta 2, V beta 3, V beta 6, or V beta 8 to levels >20% of total V bet a gene expression in nine of 15 individuals. Analysis of paired biopsy and blood specimens revealed a preferential expression of specific V beta genes, such as V beta 3, V beta 5, and V beta 8, at sites of Kvei m-Siltzbach reactions to levels four to seven times that of the corres ponding peripheral blood. Sequence analysis demonstrated that preferen tial expression of specific V beta genes at Kveim-Siltzbach reaction s ites is oligoclonal. Furthermore, the dominant V beta 8 sequence prese nt at one of the reaction sites contained a sequence motif in the vari able-diversity-joining junctional region previously identified in sarc oid lung and blood T cell populations. These results suggest that the Kveim-Siltzbach reaction is characterized by a limited TCR beta-chain repertoire consistent with an Ag-driven T cell immune response.