title: In vivo activation of Treg cells with a CD28 superagonist prevents and ameliorates chronic destructive arthritis in mice.
abstract: Although regulatory T (Treg) cells are necessary to prevent autoimmune diseases, including arthritis, whether Treg cells can ameliorate established inflammatory disease is controversial. Using the glucose-6-phosphate isomerase (G6PI)-induced arthritis model in mice, we aimed to determine the therapeutic efficacy of increasing Treg cell number and function during chronic destructive arthritis. Chronic destructive arthritis was induced by transient depletion of Treg cells prior to immunization with G6PI. At different time points after disease induction, mice were treated with a CD28 superagonistic antibody (CD28SA). CD28SA treatment during the induction phase of arthritis ameliorated the acute signs of arthritis and completely prevented the development of chronic destructive arthritis. CD28SA treatment of mice with fully developed arthritis induced a significant reduction in clinical and histological signs of arthritis. When given during the chronic destructive phase of arthritis, 56 days after disease induction, CD28SA treatment resulted in a modest reduction of clinical signs of arthritis and a reduction in histopathological signs of joint inflammation. Our data show that increasing the number and activation of Treg cells by a CD28SA is therapeutically effective in experimental arthritis.
authors.affiliation: Institute of Immunology, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Win
authors.affiliation: Department of Medicine 1-Gastroenterology, Infectious Diseases and Rheumatology and Research Centre ImmunoSciences, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Institute for Infection Immunology, Centre for Experimental and Clinical Infection Research, TWINCORE, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hünig
authors.affiliation: Institute of Immunology, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000517:prevention & control*; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D018106:CD28 Antigens / Q000819:agonists / Q000276:immunology*; D002908:Chronic Disease / Q000517:prevention & control; D004195:Disease Models, Animal; D005956:Glucose-6-Phosphate Isomerase / Q000008:administration & dosage; D007249:Inflammation / Q000517:prevention & control / Q000628:therapy; D007596:Joints / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D005956:Glucose-6-Phosphate Isomerase
keywords: Autoimmunity; Inflammation; Regulatory T cells; T helper cells