title: CD70-expressing CD4 T cells produce IFN-γ and IL-17 in rheumatoid arthritis.
abstract: OBJECTIVE
  CD70-expressing CD4 T cells are enriched in RA and promote autoimmunity via co-stimulatory CD70-CD27 interaction. This study aimed to explore the phenotype and cytokine production of CD70(+) CD4 T cells in RA.
  
  
  METHODS
  Peripheral blood mononuclear cells from 32 RA patients were isolated and frequencies of CD70(+) cells within different CD4 T subsets were analysed using flow cytometry. IFN-γ and IL-17 production were compared between the CD70(+) and CD70(-) cells. Expression of master transcription factors T-bet, GATA3 and retinoic acid-related orphan receptor gamma t (RORγt) were examined by real-time PCR. Results are presented as mean (s.e.m.).
  
  
  RESULTS
  CD4 T cells of healthy controls rarely expressed CD70 as compared with CD4 T cells of RA patients [mean 0.9% (s.e.m. 0.3%) vs 7.6 (0.6), P < 0.001]. In RA, CD70(+) cells were present within all CD4 T cell subsets, i.e. CD45RA(+)CCR7(+) naive, CD45RA(-)CCR7(+) central memory, CD45RA(-)CCR7(-) effector memory and CD45RA(+)CCR7(-) terminally differentiated effector memory T cells with a mean frequency of 3.9% (s.e.m. 1.1%), 4.0 (0.5), 4.2 (0.7) and 9.4 (4.3), respectively. As compared to CD70(-) CD4 T cells, CD70(+) CD4 T cells produced significantly more IFN-γ and IL-17 after short activation. CD70(+) CD4 T cells preferentially expressed transcription factor RORγt.
  
  
  CONCLUSIONS
  CD70(+) CD4 T cells are enriched in RA and may directly contribute to RA pathogenesis by producing IFN-γ and IL-17. Targeting CD70(+) CD4 T cells might offer new therapeutic opportunities in RA.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jin Kyun
authors.initials: JK
authors.lastname: Park
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Bobby Kwanghoon
authors.initials: BK
authors.lastname: Han
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji Ah
authors.initials: JA
authors.lastname: Park
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Youn Jung
authors.initials: YJ
authors.lastname: Woo
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Paulina
authors.initials: P
authors.lastname: Chalan
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Annemieke M
authors.initials: AM
authors.lastname: Boots
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Division of Rheumatology, Cooper Medical School, Rowan University, Camden, NJ, USA, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands and World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. ysong@snu.ac.kr.
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D053282:CD27 Ligand / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
chemical_list: D053282:CD27 Ligand; D020381:Interleukin-17; D007371:Interferon-gamma
keywords: CD17; CD4; CD70; T cells; rheumatoid arthritis