title: Inflammatory arthritis and dermatitis in thymectomized, CD25+ cell-depleted adult mice.
abstract: OBJECTIVE
  To investigate the effect of CD25+ or CTLA-4(+) cell depletion on the natural history of collagen-induced and spontaneous arthritis in male DBA1/J mice.
  
  
  METHODS
  Male DBA/1J mice were treated with anti-CD25 depleting antibody (PC61) or isotype control (GL113), or with anti-CTLA-4 depleting antibody (4F10) at various time-points peri- and post-immunization with bovine collagen type II, emulsified in adjuvant. In order to develop a model system in which long-term depletion of CD25+ regulatory T cells can be achieved prior to immunization, adult male DBA/1J mice were thymectomized prior to administration of either PC61 or GL113. An ELISA demonstrated that PC61 and GL113 antibodies were undetectable by 21 days after administration and FACS analysis confirmed the long-term depletion of CD25+ cells in peripheral blood.
  
  
  RESULTS
  In the thymectomized mice treated with PC61, the CD25+ population was depleted and a spontaneous arthritis developed (P = 0.03). In the non-thymectomized mice, administration of CTLA-4-depleting antibody prior to immunization exacerbated arthritis in mice immunized with bovine collagen type II emulsified in incomplete Freund's adjuvant (P < 0.01). However, no significant difference in the natural history of arthritis was evident in mice treated with CD25-depleting antibody (PC61) compared with control antibody (GL113).
  
  
  CONCLUSIONS
  Two separate models implicate CD25+ CTLA-4(+) constitutive cells in suppression of arthritis in susceptible DBA/1 males: exacerbation of collagen-induced arthritis following CTLA-4 depletion at the start of induction and spontaneous arthritis in the thymectomy/CD25+ depletion model.
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Cambridge, UK.
authors.forename: A
authors.initials: A
authors.lastname: Loughry
authors.forename: S
authors.initials: S
authors.lastname: Fairchild
authors.forename: N
authors.initials: N
authors.lastname: Athanasou
authors.forename: J
authors.initials: J
authors.lastname: Edwards
authors.forename: F C
authors.initials: FC
authors.lastname: Hall
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D019540:Area Under Curve; D001168:Arthritis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D003094:Collagen / Q000276:immunology; D003872:Dermatitis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005620:Freund's Adjuvant / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012720:Severity of Illness Index
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D003094:Collagen; D005620:Freund's Adjuvant