title: The effect of autoimmune arthritis treatment strategies on regulatory T-cell dynamics.
abstract: OBJECTIVE
  Since their discovery over 15 years ago, intensive research has focused on the presence, phenotype and function of FOXP3(+) regulatory T cells (Treg) in autoimmune diseases such as rheumatoid arthritis (RA). The questions of whether Treg deficiencies underlie autoimmune pathology and whether or how Treg-related therapeutic approaches might be successful are still a subject of a vivid debate. In this review we give an overview of how current therapies influence Treg numbers and function in RA and juvenile idiopathic arthritis (JIA) and discuss these findings in the light of new Treg-based intervention strategies for autoimmune arthritis.
  
  
  RESULTS
  The attempt to relate rheumatic diseases like rheumatoid arthritis and juvenile idiopathic arthritis to Treg has led to somewhat heterogeneous observations. So far, no clear defects in Treg numbers or function have been identified in autoimmune arthritis. The current standard therapies, that is methotrexate and biologicals, are generally effective, but the exact mechanism of action and their effect on Treg is not fully known. Nevertheless, the majority of in-vitro and ex-vivo data point towards a positive influence of these treatments on Treg number and function. These observations are not all consistent, however, and it is not known whether the observed effects on Treg are primary or secondary effects. To safely conduct targeted regulatory T-cell therapy in rheumatic diseases more knowledge about regulatory T-cell function in an inflammatory environment is needed that coincides with the initiative to elucidate the exact mechanism of current therapies.
authors.affiliation: Center for Molecular and Cellular Intervention, Department of Paediatric Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Gerdien
authors.initials: G
authors.lastname: Mijnheer
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
authors.forename: Femke
authors.initials: F
authors.lastname: van Wijk
mesh_terms: D000069594:Abatacept; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000276:immunology / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy*; D001685:Biological Factors / Q000627:therapeutic use; D002648:Child; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
chemical_list: D000069594:Abatacept; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001685:Biological Factors; D018796:Immunoconjugates; D053590:Interleukin 1 Receptor Antagonist Protein; D008727:Methotrexate; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; D015850:Interleukin-6; C502936:tocilizumab