Accumulation of Common Clonal T Cells in Multiple Lesions of Sarcoidosis

Abstract

T cells recognizing as yet unknown antigens (Ags) are considered to play an important role in the development and perpetuation of the disease process of sarcoidosis. Several studies have shown that T cells that bear a limited T-cell receptor (TCR) repertoire may play an important role in this disorder. However, regarding variable (V) gene repertoire usage, the results differ among various reports. One reason for such inconsistency may be due to the materials used in these studies. Most studies analyzed the T-cell repertoire in the sarcoid lung. However, clonal expansion of pulmonary T cells, probably due to the activation by inhaled exogenous Ags, was observed and such expansion may seriously influence the repertoire analysis. Reverse transcriptase-polymerase chain reaction and subsequent single-strand conformation polymorphism analysis were used for the analysis of TCR repertoire. To exclude unrelated T-cell clones, we used intramuscular sarcoid nodules and/or lymph node (LN) sarcoid lesions as our materials. We also analyzed sarcoid lesions from different organs and then compared the results. T cells of the same clonality were found to exist in widely separated sites in intramuscular and LN sarcoid lesions in almost all Vbeta subfamilies. Identical T-cell clones were present in the sarcoid lesions from different organs in several Vbeta subfamilies. Some of the common T-cell clones in separated sites in intramuscular and LN sarcoid lesions and in sarcoid samples from different organs may recognize Ags that are related to the pathogenesis of sarcoidosis.