title: Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127(low) Treg Cells in Patients With Chronic Rheumatoid Arthritis.
abstract: OBJECTIVE
  Conflicting evidence exists regarding the suppressive capacity of Treg cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA). The aim of this study was to determine whether Treg cells are intrinsically defective in RA.
  
  
  METHODS
  Using a range of assays on PB samples from patients with chronic RA and healthy controls, CD3+CD4+CD25+CD127(low) Treg cells from the CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine expression (ex vivo and after in vitro stimulation), suppression of Teff cell proliferation and cytokine production, suppression of monocyte-derived cytokine/chemokine production, and gene expression profiles.
  
  
  RESULTS
  No differences between RA patients and healthy controls were observed with regard to the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or CD161), or proinflammatory cytokine profile (interleukin-17 [IL-17], interferon-γ [IFNγ], or tumor necrosis factor [TNF]). FoxP3 expression was slightly increased in Treg cells from RA patients. The ability of Treg cells to suppress the proliferation of T cells or the production of cytokines (IFNγ or TNF) upon coculture with autologous CD45RO+ Teff cells and monocytes was not significantly different between RA patients and healthy controls. In PB samples from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress the production of certain cytokines/chemokines (IL-1β, IL-1 receptor antagonist, IL-7, CCL3, or CCL4) by autologous lipopolysaccharide-activated monocytes. However, this was not observed in all patients, and other cytokines/chemokines (TNF, IL-6, IL-8, IL-12, IL-15, or CCL5) were generally suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells from the PB revealed no statistically significant differences between RA patients and healthy controls.
  
  
  CONCLUSIONS
  Our findings indicate that there is no global defect in either CD45RO+ or CD45RA+ Treg cells in the PB of patients with chronic RA.
authors: King's College London, London, UK.
authors: Gina J
authors: GJ
authors: Walter
authors: King's College London, London, UK.
authors: Veerle
authors: V
authors: Fleskens
authors: Novo Nordisk, Måløv, Denmark.
authors: Klaus S
authors: KS
authors: Frederiksen
authors: King's College London, London, UK.
authors: Megha
authors: M
authors: Rajasekhar
authors: Guy's and St. Thomas' NHS Foundation Trust, London, UK.
authors: Bina
authors: B
authors: Menon
authors: Novo Nordisk, Måløv, Denmark.
authors: Jens G
authors: JG
authors: Gerwien
authors: King's College London, London, UK.
authors: Hayley G
authors: HG
authors: Evans
authors: King's College London, London, UK.
authors: Leonie S
authors: LS
authors: Taams
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; C508609:IL10 protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens