Abstract
Sarcoidosis is a multiorgan granulomatous disorder of unknown etiology characterized by noncaseating granulomas in involved tissues. A positive Kveim-Siltzbach reaction is a granulomatous response to an intradermal injection of a suspension of sarcoid tissue extract in individuals with sarcoidosis. The protracted time course and granulomatous features of this reaction have a striking resemblance to the Mitsuda reaction in tuberculous leprosy, which suggests that the Kveim-Siltzbach reaction is a response to an unknown Ag(s). To evaluate whether this reaction is Ag-driven, an analysis of the TCR Vβ repertoire in 15 Kveim-Siltzbach reaction sites was performed using a PCR technique and primers specific for 20 Vβ gene families. Results of this analysis demonstrated a pattern of Vβ expression dominated by expression of Vβ2, Vβ3, Vβ6, or Vβ8 to levels >20% of total Vβ gene expression in nine of 15 individuals. Analysis of paired biopsy and blood specimens revealed a preferential expression of specific Vβ genes, such as Vβ3, Vβ5, and Vβ8, at sites of Kveim-Siltzbach reactions to levels four to seven times that of the corresponding peripheral blood. Sequence analysis demonstrated that preferential expression of specific Vβ genes at Kveim- Siltzbach reaction sites is oligoclonal. Furthermore, the dominant Vβ8 sequence present at one of the reaction sites contained a sequence motif in the variable-diversity-joining junctional region previously identified in sarcoid lung and blood T cell populations. These results suggest that the Kveim-Siltzbach reaction is characterized by a limited TCR β-chain repertoire consistent with an Ag-driven T cell immune response.
Original language | English (US) |
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Pages (from-to) | 1450-1460 |
Number of pages | 11 |
Journal | Journal of Immunology |
Volume | 154 |
Issue number | 3 |
State | Published - 1995 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology