Single cell analysis of T cells infiltrating labial salivary glands from patients with Sjögren's syndrome.
Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into the lacrimal and salivary glands leading to symptomatic dry eyes and mouth. To analyze the function of T cells infiltrating the labial salivary glands, we analyzed T cell receptor (TCR) beta and alpha chains, the expression of various cytokine mRNAs, and apoptosis associated genes in predominant TCR BV2+ T cells in the labial salivary glands of patients with SS at the single cell level. TCR BV2+ T cells in the labial salivary glands were sorted as single cells by flow-cytometry, and then examined by a single cell polymerase chain reaction (PCR). We isolated 18 TCR BV2+ T cell clones from three patients with SS. In six clones, there were highly conserved amino acid motifs (RDxG, GNT, QGxxQETQ) in the CDR3 region of the TCR beta chain. Three of the six clones showed conserved amino acids (EDxTG, or ExxTG) in the CDR3 region of the TCR alpha chain, suggesting restricted T cell epitopes. All TCR BV2+ clones expressed IL-2 mRNA, and six clones were able to produce IL-4, indicating that the cells were Th0 type T cells. All TCR BV2+ clones in the labial salivary glands were CD4+ T cells, and ten clones overexpressed Fas antigen at the mRNA level. In contrast, only one clone expressed Fas-ligand (Fas-L) mRNA, and neither perforin nor granzyme A/B was expressed. In conclusion, these findings support the notion that TCR BV2+ T cells that infiltrate labial salivary glands recognize restricted epitopes and function as CD4+ Th0 type T cells in the induction phase of autoimmunity.
Matsumoto
I
I
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki 305-8575, Japan.
Okada
S
S
Kuroda
K
K
Iwamoto
I
I
Saito
Y
Y
Tokuhisa
T
T
Nishioka
K
K
Sumida
T
T
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D018450:Disease Progression; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012469:Salivary Glands / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D017931:DNA Primers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor