{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T05:55:39Z","timestamp":1719813339066},"reference-count":43,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Multiple Sclerosis International"],"published-print":{"date-parts":[[2011]]},"abstract":"<jats:p>Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-onset thymic involution that causes reduced thymic output. The reduced thymic output leads to secondary peripheral homeostatic alterations in na\u00efve CD4 T-cells, which closely mimic T-cell alterations observed in an experimental animal model of diabetes mellitus. Homeostatic T-cell receptor (TCR) signalling and proliferation of na\u00efve T cells are induced by self-peptides. Consequently, the findings of increased TCR signalling of na\u00efve CD4 T-cells, without increased proliferation, in PPMS, and the increased homeostatic proliferation of na\u00efve CD4 T-cells in RRMS favour the development of autoimmunity. Thus, it seems highly likely that peripheral T-cell alterations secondary to a thymic abnormality contribute to the pathogenesis of both MS subtypes.<\/jats:p>","DOI":"10.1155\/2011\/461304","type":"journal-article","created":{"date-parts":[[2011,9,21]],"date-time":"2011-09-21T07:51:29Z","timestamp":1316591489000},"page":"1-6","source":"Crossref","is-referenced-by-count":8,"title":["Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis"],"prefix":"10.1155","volume":"2011","author":[{"given":"David G.","family":"Haegert","sequence":"first","affiliation":[{"name":"Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, QC, Canada H3A 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