title: Proteoglycan aggrecan conducting T cell activation and apoptosis in a murine model of rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s) in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG) aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA), and CD4(+) T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.
authors.affiliation: Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, Szigeti u. 12, Pecs 7624, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Hanyecz
authors.affiliation: Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, Szigeti u. 12, Pecs 7624, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Olasz
authors.affiliation: Department of Medical Biology, University of Pecs, Szigeti u. 12, Pecs 7624, Hungary.
authors.forename: O
authors.initials: O
authors.lastname: Tarjanyi
authors.affiliation: Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, Szigeti u. 12, Pecs 7624, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Nemeth
authors.affiliation: Section of Molecular Medicine, Department of Orthopedic Surgery, Rush University Medical Center, 1735 W. Harrison Street, Chicago, IL 60612, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mikecz
authors.affiliation: Section of Molecular Medicine, Department of Orthopedic Surgery, Rush University Medical Center, 1735 W. Harrison Street, Chicago, IL 60612, USA.
authors.forename: T T
authors.initials: TT
authors.lastname: Glant
authors.affiliation: Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, Szigeti u. 12, Pecs 7624, Hungary.
authors.forename: F
authors.initials: F
authors.lastname: Boldizsar
mesh_terms: D053674:Aggrecans / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D053674:Aggrecans; D018984:Epitopes, T-Lymphocyte