title: CD4+ PD-1+ T cells accumulate as unique anergic cells in rheumatoid arthritis synovial fluid.
abstract: OBJECTIVE
  The PD-1 receptor, whose deficiency in mice causes autoimmune diseases such as arthritis, is considered to be a negative regulator of activated T cells and to play a crucial role in peripheral tolerance. To clarify the involvement of the PD-1 system in rheumatoid arthritis (RA), we investigated PD-1 expression on synovial fluid (SF) T cells from patients with RA.
  
  
  METHODS
  FACS analysis for PD-1 was performed on SF T cells from 44 patients with RA and 6 with osteoarthritis (OA), and also on peripheral blood (PB) T cells from 12 RA patients and 7 healthy controls. Two-color analysis of cell surface PD-1 expression and the intracellular concentration of cytokine production was used to investigate CD4+ T cells from SF of patients with RA and PB from controls.
  
  
  RESULTS
  Scarcely any PD-1 expression was detected on control PB T or OA SF T cells. In contrast, PD-1+ cells made up 20.9 +/- 8.6% (mean +/- SD) of RA SF T cells. In RA SF, PD-1 was expressed more predominantly on CD4+ T cells than on CD8+ T cells. As well as expressing CD45RO and CXCR3, CD4+ PD-1+ T cells were mostly CTLA-4 positive and CD26 negative, and were enriched in CD45RB(low) cells. Intracellular cytokine staining revealed that CD4+ PD-1+, but not CD4+ PD-1-, T cells produced interleukin 10 (IL-10), and that CD4+ PD-1+ T cells produced less IL-2 than CD4+ PD-1- T cells.
  
  
  CONCLUSIONS
  PD-1+ T cells in RA SF are enriched, and phenotypic analysis suggests that these cells constitute a unique anergic T cell subset in RA SF.
authors.affiliation: Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Hatachi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwai
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawano
authors.forename: Sahoko
authors.initials: S
authors.lastname: Morinobu
authors.forename: Masaya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Koshiba
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Saura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kumagai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D017635:Clonal Anergy; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D007376:Interleukin-2; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins; D016753:Interleukin-10