title: Tumor necrosis factor receptor type I expression of CD4+ T cells in rheumatoid arthritis enables them to follow tumor necrosis factor gradients into the rheumatoid synovium.
abstract: OBJECTIVE
  The cytokine tumor necrosis factor (TNF) plays a central role in the pathogenesis of rheumatoid arthritis (RA), but its disease-specific effector mechanisms have not been fully elucidated. This study was undertaken to investigate the role of TNF in T cell accumulation and migration in the synovitic joints of RA patients.
  
  
  METHODS
  Vital tissue sections from rheumatoid synovium were generated using a horizontally oscillating microtome and were coincubated with fluorescence-labeled CD4+ T cells. Migration was detected by fluorescence and confocal microscopy. Migrating T cells were recovered from the tissue and analyzed for phenotype. Chemotaxis of CD4+ T cells from RA patients in response to increasing concentrations of TNF was analyzed in Transwell experiments.
  
  
  RESULTS
  CD4+ T cells from RA patients migrated into the tissue sections in significantly higher numbers than T cells from healthy controls. Migrating CD4+ T cells differed from nonmigrating ones in their increased expression of TNF receptor type I (TNFRI), which was expressed on a fraction of circulating CD4+ T cells from RA patients, but not from controls. CD4+ T cells from the peripheral blood of RA patients were also found to migrate along TNF concentration gradients ex vivo. Accordingly, blockade of either TNF or TNFRI nearly abrogated in vitro T cell migration in synovial tissue.
  
  
  CONCLUSIONS
  Our findings indicate that the interaction of TNF with TNFRI is pivotal for T cell migration in synovial tissue in vitro, and thereby suggest a relevant role of the cytokine for in vivo T cell trafficking to synovitic joints.
authors.affiliation: University of Leipzig, Leipzig, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Rossol
authors.forename: Kristin
authors.initials: K
authors.lastname: Schubert
authors.forename: Undine
authors.initials: U
authors.lastname: Meusch
authors.forename: Anett
authors.initials: A
authors.lastname: Schulz
authors.forename: Bernd
authors.initials: B
authors.lastname: Biedermann
authors.forename: Jens
authors.initials: J
authors.lastname: Grosche
authors.forename: Matthias
authors.initials: M
authors.lastname: Pierer
authors.forename: Roger
authors.initials: R
authors.lastname: Scholz
authors.forename: Christoph
authors.initials: C
authors.lastname: Baerwald
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hagen
authors.forename: Ulf
authors.initials: U
authors.lastname: Wagner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018929:Cell Culture Techniques; D054441:Cell Migration Assays, Leukocyte; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I