title: CD4+ T cells recognizing a single self-peptide expressed by APCs induce spontaneous autoimmune arthritis.
abstract: We have examined processes leading to the spontaneous development of autoimmune inflammatory arthritis in transgenic mice containing CD4+ T cells targeted to a nominal Ag (hemagglutinin (HA)) and coexpressing HA driven by a MHC class II promoter. Despite being subjected to multiple tolerance mechanisms, autoreactive CD4+ T cells accumulate in the periphery of these mice and promote systemic proinflammatory cytokine production. The majority of mice spontaneously develop inflammatory arthritis, which is accompanied by an enhanced regional immune response in lymph nodes draining major joints. Arthritis development is accompanied by systemic B cell activation; however, neither B cells nor Ab is required for arthritis development, since disease develops in a B cell-deficient background. Moreover, arthritis also develops in a recombinase activating gene-deficient background, indicating that the disease process is driven by CD4+ T cells recognizing the neo-self HA Ag. These findings show that autoreactive CD4+ T cells recognizing a single self-Ag, expressed by systemically distributed APCs, can induce arthritis via a mechanism that is independent of their ability to provide help for autoantibody production.
authors.affiliation: The Wistar Institute, Department of Surgery, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Rankin
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Reed
authors.forename: Soyoung
authors.initials: S
authors.lastname: Oh
authors.forename: Cristina
authors.initials: C
authors.lastname: Cozzo Picca
authors.forename: Heath M
authors.initials: HM
authors.lastname: Guay
authors.forename: Joseph
authors.initials: J
authors.lastname: Larkin
authors.forename: Laura
authors.initials: L
authors.lastname: Panarey
authors.forename: Malinda K
authors.initials: MK
authors.lastname: Aitken
authors.forename: Brigitte
authors.initials: B
authors.lastname: Koeberlein
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: John E
authors.initials: JE
authors.lastname: Tomaszewski
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D001168:Arthritis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D011401:Promoter Regions, Genetic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D001324:Autoantigens; D006388:Hemagglutinins; D015395:Histocompatibility Antigens Class I; D010455:Peptides