{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:19:19Z","timestamp":1773674359798,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although therapies targeting distinct cellular pathways (e.g., anticytokine versus anti\u2013B cell therapy) have been found to be an effective strategy for at least some patients with inflammatory arthritis, the mechanisms that determine which pathways promote arthritis development are poorly understood. We have used a transgenic mouse model to examine how variations in the CD4+ T cell response to a surrogate self-peptide can affect the cellular pathways that are required for arthritis development. CD4+ T cells that are highly reactive with the self-peptide induce inflammatory arthritis that affects male and female mice equally. Arthritis develops by a B cell\u2013independent mechanism, although it can be suppressed by an anti-TNF treatment, which prevented the accumulation of effector CD4+ Th17 cells in the joints of treated mice. By contrast, arthritis develops with a significant female bias in the context of a more weakly autoreactive CD4+ T cell response, and B cells play a prominent role in disease pathogenesis. In this setting of lower CD4+ T cell autoreactivity, B cells promote the formation of autoreactive CD4+ effector T cells (including Th17 cells), and IL-17 is required for arthritis development. These studies show that the degree of CD4+ T cell reactivity for a self-peptide can play a prominent role in determining whether distinct cellular pathways can be targeted to prevent the development of inflammatory arthritis.<\/jats:p>","DOI":"10.4049\/jimmunol.1302528","type":"journal-article","created":{"date-parts":[[2014,3,4]],"date-time":"2014-03-04T03:20:30Z","timestamp":1393903230000},"page":"3043-3056","source":"Crossref","is-referenced-by-count":8,"title":["The Degree of CD4+ T Cell Autoreactivity Determines Cellular Pathways Underlying Inflammatory Arthritis"],"prefix":"10.1093","volume":"192","author":[{"given":"Olivia A","family":"Perng","sequence":"first","affiliation":[{"name":"The Wistar Institute , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malinda","family":"Aitken","sequence":"additional","affiliation":[{"name":"The Wistar Institute , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew L","family":"Rankin","sequence":"additional","affiliation":[{"name":"The Wistar Institute , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Garcia","sequence":"additional","affiliation":[{"name":"The Wistar Institute , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Kropf","sequence":"additional","affiliation":[{"name":"The Wistar Institute , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Erikson","sequence":"additional","affiliation":[{"name":"The Wistar Institute , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S","family":"Garlick","sequence":"additional","affiliation":[{"name":"The Wistar Institute , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J","family":"Caton","sequence":"additional","affiliation":[{"name":"The Wistar Institute , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,4,1]]},"reference":[{"key":"2025032404215831300_r1","first-page":"655","volume-title":"Pathophysiology of Disease an Introduction to Clinical Medicine","author":"Gelber","year":"2010","edition":"6th"},{"key":"2025032404215831300_r2","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. 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