title: Amelioration of experimental arthritis by stroke-induced immunosuppression is independent of Treg cell function.
abstract: OBJECTIVE
  Clinical evidence suggests that neurological lesions can protect from arthritis. Acute cerebral ischaemia induces severe immunosuppression, resulting in enhanced susceptibility to infections. We aimed to determine if stroke-induced immunosuppression can ameliorate arthritis and to delineate the immunological mechanisms involved.
  
  
  METHODS
  Unilateral cerebral ischaemia was induced in mice by occlusion of one middle cerebral artery (MCAO) at different time points after induction of G6PI-induced arthritis in mice. Clinical and histological signs of arthritis were assessed. Regulatory T cells were specifically depleted by injection of diphtheria toxin into transgenic DEREG mice. Immunological correlates of MCAO were determined by flow cytometry and serological methods.
  
  
  RESULTS
  MCAO reduced the clinical and histological signs of arthritis significantly. To be effective, stroke had to be induced during the induction phase or the early clinical stage of arthritis. MCAO induced a global loss of leucocytes. Despite the reduced absolute number of lymphocytes, the functional differentiation of T helper cells into Th1/17 cells and the production of autoantibodies were unimpaired. Depletion experiments showed that regulatory T cells were dispensable for the protective effect of MCAO.
  
  
  CONCLUSIONS
  MCAO ameliorates arthritis. The correlate of protection from arthritis is not the reduction of a particular pathogenic leucocyte subset or the preferential expansion or emergence of a protective cell population but the global reduction of leucocytes during arthritis.
authors: Institute of Immunology, University Hospital Jena, Jena, Germany.
authors: Ingo M
authors: IM
authors: Irmler
authors: Institute of Pathology, University Hospital Jena, Jena, Germany.
authors: Mieczyslaw
authors: M
authors: Gajda
authors: Institute of Immunology, University Hospital Jena, Jena, Germany.
authors: Thomas
authors: T
authors: Kamradt
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D002545:Brain Ischemia / Q000276:immunology; D002454:Cell Differentiation; D007108:Immune Tolerance / Q000276:immunology*; D016867:Immunocompromised Host / Q000276:immunology*; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D065840:Protective Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D001323:Autoantibodies
keywords: Arthritis; Inflammation; T Cells