title: Monocytes are essential for inhibition of synovial T-cell glucocorticoid-mediated apoptosis in rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is characterized by synovial inflammation with local accumulation of mononuclear cells such as macrophages and lymphocytes. We previously demonstrated that intra-articular glucocorticoids decrease the synovial tissue (ST) T-cell population and therefore aimed to investigate whether this is mediated through modulation of apoptosis.
  
  
  METHODS
  Apoptosis and cell phenotype were evaluated by immunohistochemistry and dual-immunofluorescence in synovial biopsy sections from 12 RA patients before and after a mean of 11 days of an intra-articular triamcinolone knee injection. In vitro, RA synovial fluid (SF)-derived T cells were evaluated for Annexin V expression by multicolor flow cytometry after 24-hour exposure to dexamethasone, methylprednisolone, or triamcinolone. We also tested induction of apoptosis by dexamethasone on psoriatic arthritis SF-derived T cells using the same method.
  
  
  RESULTS
  Intra-articular glucocorticoids reduced ST T cells but not macrophage number. ST apoptosis levels were unchanged following treatment, virtually absent from lymphoid aggregates, and minimal in CD3+ cells both before and after treatment. RA SF T cells were resistant to glucocorticoid-induced apoptosis when cultured in the presence of monocytes but were rendered sensitive to all three tested compounds upon SF isolation. Furthermore, transwell coculture of monocytes and T cells demonstrated that soluble factor(s) and not cellular contact are essential for T-cell resistance to glucocorticoid-mediated apoptosis. This feature is RA-specific as far as dexamethasone-induced apoptosis in nonisolated SF T cells obtained from psoriatic arthritis patients is concerned.
  
  
  CONCLUSIONS
  We demonstrate that monocytes rescue synovial T cells from glucocorticoid-induced apoptosis, a feature that is specific for RA. To overcome this, we propose the use of monocyte-targeted therapies rather than T-cell apoptosis-inducing therapies.
authors.affiliation: Department of Rheumatology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden. dimitris.makrygiannakis@ki.se
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Makrygiannakis
authors.forename: Shankar
authors.initials: S
authors.lastname: Revu
authors.forename: Petra
authors.initials: P
authors.lastname: Neregård
authors.forename: Erik
authors.initials: E
authors.lastname: af Klint
authors.forename: Omri
authors.initials: O
authors.lastname: Snir
authors.forename: Cecilia
authors.initials: C
authors.lastname: Grundtman
authors.forename: Anca Irinel
authors.initials: AI
authors.lastname: Catrina
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005938:Glucocorticoids / Q000633:toxicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D013582:Synovial Fluid / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D005938:Glucocorticoids