{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T22:53:45Z","timestamp":1769640825123,"version":"3.49.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"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":[[2010,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Age-related changes in immune regulation are likely to account for the age-associated increase in serum autoantibody levels and in certain autoimmune disorders, such as myasthenia gravis (MG). To demonstrate directly a loss of immune tolerance in older individuals, responses to the acetylcholine receptor, the autoantigen in MG, were assessed in transgenic mice expressing the Torpedo californica acetylcholine receptor (TAChR) \u03b1-chain as a neo-self Ag. T cells from young transgenic mice had been shown to be tolerant to p146\u2013162, the TAChR \u03b1-chain peptide that dominated young nontransgenic T cell responses in vitro. The immunodominance of p146\u2013162 was not lost with age; fine specificity was preserved. Moreover, T cell tolerance to p146\u2013162, as well as to other epitopes of the TAChR \u03b1-chain extracellular domain, was maintained in old transgenic mice. Even multiple TAChR immunizations coupled with the MG-enhancing cytokine, IL-12, did not break tolerance. In addition, T cells exhibiting CD4 upregulation, an early activation marker, were reduced in frequency equivalently in old and young transgenic animals, suggesting that immune regulation in this model was not impacted by aging. Moreover, B cell tolerance was also maintained with age. The persistence of immune tolerance was accompanied by an increase in the proportion of T regulatory cells; it is speculated that this may compensate for deficiencies in central tolerance that occur owing to thymic involution. In summary, our study reveals, for the first time, that some immune tolerance mechanisms do survive aging; this suggests that certain late-onset autoimmune disorders may be induced by a specific insult that disrupts immune homeostasis.<\/jats:p>","DOI":"10.4049\/jimmunol.0901618","type":"journal-article","created":{"date-parts":[[2010,4,30]],"date-time":"2010-04-30T22:16:05Z","timestamp":1272665765000},"page":"6067-6075","source":"Crossref","is-referenced-by-count":8,"title":["Maintenance of Immune Tolerance to a Neo-Self Acetylcholine Receptor Antigen with Aging: Implications for Late-Onset Autoimmunity"],"prefix":"10.1093","volume":"184","author":[{"given":"Sue","family":"Stacy","sequence":"first","affiliation":[{"name":"Department of Cellular and Structural Biology"},{"name":"The Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio , San Antonio, TX 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Earlanda L","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan E","family":"Standifer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Pasquali","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A","family":"Krolick","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J","family":"Infante","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Kraig","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology"},{"name":"The Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio , San Antonio, TX 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,6,1]]},"reference":[{"key":"2026012806265809800_r1","first-page":"557","article-title":"High prevalence of anti-cardiolipin and other autoantibodies in a healthy elderly population.","volume":"69","author":"Manoussakis","year":"1987","journal-title":"Clin. 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