title: A distinct human CD4+ T cell subset that secretes CXCL13 in rheumatoid synovium.
abstract: OBJECTIVE
  A subset of CD4+ T cells in the synovium of patients with rheumatoid arthritis (RA) produce CXCL13, a chemokine that is crucial for the formation of germinal centers. This study was undertaken to determine the relevance of this population to known subsets of T helper cells and to proinflammatory cytokines, and how these cells are generated.
  
  
  METHODS
  The expression of Th markers and CXCL13 by CD4+ T cells in RA synovium and the involvement of proinflammatory cytokines in CXCL13 production were assessed. We also investigated whether CXCL13+CD4+ T cells could be newly induced.
  
  
  RESULTS
  CXCL13+CD4+ T cells in RA synovium were negative for interferon-γ (IFNγ), interleukin-4 (IL-4), IL-17, FoxP3, and CXCR5 and expressed low levels of inducible T cell costimulator, indicating that this population is a distinct human CD4 subset. T cell receptor (TCR) stimulation of CD4+ T cells, obtained from RA synovium with low expression of CXCL13, promptly induced CXCL13 production and addition of proinflammatory cytokines supported the long-term production of CXCL13. These findings indicate that CXCL13-producing CD4+ T cells can be in a memory state ready to be reactivated upon TCR stimulation and that proinflammatory cytokines are involved in persistent CXCL13 production. TCR stimulation of CD4+ T cells from the blood of healthy volunteers, together with proinflammatory cytokine supplementation, induced a population that produced CXCL13, but not IFNγ. Synovial T cells recruited CXCR5+ cells in a CXCL13-dependent manner.
  
  
  CONCLUSIONS
  CXCL13-producing CD4+ T cells induced in RA synovium may play a role in the recruitment of CXCR5+ cells, such as B cells and circulating follicular helper T cells, and in ectopic lymphoid neogenesis at sites of inflammation.
authors.affiliation: Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Shio
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Murata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shibuya
authors.forename: Mami
authors.initials: M
authors.lastname: Morita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Furu
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ito
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
authors.forename: Shuichi
authors.initials: S
authors.lastname: Matsuda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshitomi
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D054382:Chemokine CXCL13 / Q000378:metabolism*; D002633:Chemotaxis / Q000276:immunology; D006801:Humans; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
chemical_list: D054382:Chemokine CXCL13