title: Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients.
abstract: Rheumatoid arthritis (RA) is an autoimmune destructive arthritis associated with CD4(+) T cell-mediated immunity. Although expanded CD4(+) T cell clones (ECs) has already been confirmed, the detailed characteristics of ECs have not been elucidated in RA. Using combination of a single-cell analysis and next-generation sequencing (NGS) in TCR repertoire analysis, we here revealed the detailed nature of ECs by examining peripheral blood (PB) from 5 RA patients and synovium from 1 RA patient. When we intensively investigated the single-cell transcriptome of the most expanded clones in memory CD4(+) T cells (memory-mECs) in RA-PB, senescence-related transcripts were up-regulated, indicating circulating ECs were constantly stimulated. Tracking of the transcriptome shift within the same memory-mECs between PB and the synovium revealed the augmentations in senescence-related gene expression and the up-regulation of synovium-homing chemokine receptors in the synovium. Our in-depth characterization of ECs in RA successfully demonstrated the presence of the specific immunological selection pressure, which determines the phenotype of ECs. Moreover, transcriptome tracking added novel aspects to the underlying sequential immune processes. Our approach may provide new insights into the pathophysiology of RA.
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ishigaki
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shoda
authors.affiliation: Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kochi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Yuho
authors.initials: Y
authors.lastname: Kadono
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Fujio
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology
chemical_list: D011948:Receptors, Antigen, T-Cell; D019707:Receptors, Chemokine