TCR in Fas-sensitive T cells from labial salivary glands of patients with Sjögren's syndrome.
Apoptosis is found in labial salivary glands of patients with Sjogren's syndrome (SS). To analyze the pathogenesis of apoptosis in labial salivary glands of SS patients, we examined the expression of Fas Ag and Fas ligand (FasL) 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. FasL is over-expressed specifically on T cells infiltrating into the labial salivary glands as seen by an reverse transcription-PCR method. These results suggest that apoptosis in SS lips is mediated by a Fas/FasL pathway. PCR single-strand conformation polymorphism (SSCP) clearly demonstrated that more than 40% of the T cells accumulated in labial salivary glands are deleted by incubation with CH-11 for 24 h in vitro, indicating that these expanded cells are Fas sensitive. junctional sequence analysis showed that the same conserved amino acid motifs (LAGG, RLA, SLG, QGPG, PGG, GGE, RGR, KPG, AGD, and MLG) 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 autoantigens. In conclusion, the findings suggest that Fas-sensitive T cells in labial salivary glands of SS patients are generated by Ag stimulation and might function as autoreactive T cells.
Sumida
T
T
Division of Rheumatology and Molecular Immunology, Institute of Medical Science, St. Marianna University, School of Medicine, Kawasaki, Japan.
Matsumoto
I
I
Murata
H
H
Namekawa
T
T
Matsumura
R
R
Tomioka
H
H
Iwamoto
I
I
Saito
Y
Y
Mizushima
Y
Y
Hasunuma
T
T
Maeda
T
T
Nishioka
K
K
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D053222:Fas Ligand Protein; D006801:Humans; D008024:Ligands; D008046:Lip / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D012470:Salivary Glands, Minor / Q000166:cytology* / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D019014:fas Receptor / Q000494:pharmacology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor