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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.<\/jats:p>","DOI":"10.4049\/jimmunol.180.2.833","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:09:13Z","timestamp":1397862553000},"page":"833-841","source":"Crossref","is-referenced-by-count":22,"title":["CD4+ T Cells Recognizing a Single Self-Peptide Expressed by APCs Induce Spontaneous Autoimmune Arthritis"],"prefix":"10.1093","volume":"180","author":[{"given":"Andrew L","family":"Rankin","sequence":"first","affiliation":[{"name":"The Wistar Institute, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy J","family":"Reed","sequence":"additional","affiliation":[{"name":"The Wistar Institute, University of Pennsylvania Medical Center , Philadelphia, PA 19104"},{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoung","family":"Oh","sequence":"additional","affiliation":[{"name":"The Wistar Institute, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Cozzo Picca","sequence":"additional","affiliation":[{"name":"The Wistar Institute, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heath M","family":"Guay","sequence":"additional","affiliation":[{"name":"The Wistar Institute, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Joseph","family":"Larkin","sequence":"additional","affiliation":[{"name":"The Wistar Institute, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Panarey","sequence":"additional","affiliation":[{"name":"The Wistar Institute, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malinda K","family":"Aitken","sequence":"additional","affiliation":[{"name":"The Wistar Institute, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Koeberlein","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E","family":"Lipsky","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E","family":"Tomaszewski","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Naji","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Caton","sequence":"additional","affiliation":[{"name":"The Wistar Institute, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,1,15]]},"reference":[{"key":"2025032610020930800_R1","first-page":"2029","volume-title":"Harrison\u2019s Principles of Internal Medicine","year":"2005"},{"key":"2025032610020930800_R2","first-page":"1968","volume-title":"Harrison\u2019s Principles of Internal Medicine","year":"2005"},{"key":"2025032610020930800_R3","first-page":"389","volume-title":"Autoimmun. 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