TCR IN FAS-SENSITIVE T-CELLS FROM LABIAL SALIVARY-GLANDS OF PATIENTS WITH SJOGRENS-SYNDROME

Apoptosis is found in labial salivary glands of patients with Sjogren' s syndrome (SS). To analyze the pathogenesis of apoptosis in labial sa livary glands of SS patients, we examined the expression of Fas Ag and Pas ligand (Fast) and TCR on T cells susceptible to;anti-fas mAbs (CH -11). Fas Ag is expressed on epithelial cells and mononuclear cells in the salivary glands as observed by an immunohistochemical method. Fas t is over-expressed specifically on T cells infiltrating into the labi al salivary glands as seen by an reverse transcription-PCR method. The se results suggest that apoptosis in SS lips is mediated by a Fas/FasL pathway. PCR single-strand conformation polymorphism (SSCP) clearly d emonstrated that more than 40% of the T cells accumulated in labial sa livary glands are deleted by incubation with CH-lf for 24 h in vitro, indicating that these expanded cells are Fas sensitive. Junctional seq uence analysis showed that the same conserved amino acid motifs (LAGG, RLA, SLG, QGPG, PGG, GGE, RGR, KPC, AGD, and MLC) in complementarity determining region 3 (CDR3) are found in Fas-sensitive T cell clones, whereas they are not detected in Fas-resistant clones, suggesting that Fas-sensitive T cells recognize restricted T cell epitopes on autoant igens. In conclusion, the findings suggest that Fas-sensitive T cells in labial salivary glands of SS patients are generated by Ag stimulati on and might function as autoreactive T cells.