Jt. Klein et al., SELECTION OF OLIGOCLONAL V-BETA-SPECIFIC T-CELLS IN THE INTRADERMAL RESPONSE TO KVEIM-SILTZBACH REAGENT IN INDIVIDUALS WITH SARCOIDOSIS, The Journal of immunology, 154(3), 1995, pp. 1450-1460
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.