{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:54:14Z","timestamp":1790171654512,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,11,15]],"date-time":"2011-11-15T00:00:00Z","timestamp":1321315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21MH087849"],"award-info":[{"award-number":["R21MH087849"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>\n                    Abnormalities in T\u2010lymphocyte populations and function are observed in autism. Soluble amyloid precursor protein \u03b1 (sAPP\u2010\u03b1) is elevated in some patients with autism and is known to be produced by immune cells. In light of the well\u2010established role of sAPP\u2010\u03b1 in proliferation, growth, and survival of neurons, we hypothesized an analogous role in the immune system. Thus, we explored whether sAPP\u2010\u03b1 could modulate immune development and function, especially aspects of the pinnacle cell of the adaptive arm of the immune system: the T cell. To do this, we generated mice overexpressing human sAPP\u2010\u03b1 and characterized elements of T\u2010cell development, signal transduction, cytokine production, and innate\/adaptive immune functions. Here, we report that transgenic sAPP\u2010\u03b1\u2010overexpressing (TgsAPP\u2010\u03b1) mice displayed increased proportions of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, while effector memory T cells were decreased in the thymus. Overall apoptotic signal transduction was decreased in the thymus, an effect that correlated with dramatic elevations in Notch1 activation; while active\u2010caspase\u20103\/total\u2010caspase\u20103 and Bax\/Bcl\u20102 ratios were decreased. Greater levels of IFN\u2010\u03b3, IL\u20102, and IL\u20104 were observed after\n                    <jats:italic>ex vivo<\/jats:italic>\n                    challenge of TgsAPP\u2010\u03b1 mouse splenocytes with T\u2010cell mitogen. Finally, after immunization, splenocytes from TgsAPP\u2010\u03b1 mice displayed decreased levels IFN\u2010\u03b3, IL\u20102, and IL\u20104, as well as suppressed ZAP70 activation, after recall antigen stimulation. Given elevated levels of circulating sAPP\u2010\u03b1 in some patients with autism, sAPP\u2010\u03b1 could potentially drive aspects of immune dysfunction observed in these patients, including dysregulated T\u2010cell apoptosis, aberrant PI3K\/AKT signaling, cytokine alterations, and impaired T\u2010cell recall stimulation.\u2014Bailey, A. R., Hou, H., Obregon, D. F., Tian, J., Zhu, Y., Zou, Q., Nikolic, W. V., Bengtson, M., Mori, T., Murphy, T., Tan, J. Aberrant T\u2010lymphocyte development and function in mice overexpressing human soluble amyloid precursor protein\u2010\u03b1: implications for autism.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 1040\u20101051 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-195438","type":"journal-article","created":{"date-parts":[[2011,11,16]],"date-time":"2011-11-16T13:35:05Z","timestamp":1321450505000},"page":"1040-1051","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Aberrant T\u2010lymphocyte development and function in mice overexpressing human soluble amyloid precursor protein\u2010\u03b1: implications for autism"],"prefix":"10.1096","volume":"26","author":[{"given":"Antoinette R.","family":"Bailey","sequence":"first","affiliation":[{"name":"Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center Department of Psychiatry and Neurosciences All Children's Hospital College of Medicine University of South Florida Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayan","family":"Hou","sequence":"additional","affiliation":[{"name":"Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center Department of Psychiatry and Neurosciences All Children's Hospital College of Medicine University of South Florida Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demian F.","family":"Obregon","sequence":"additional","affiliation":[{"name":"Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center Department of Psychiatry and Neurosciences All Children's Hospital College of Medicine University of South Florida Tampa Florida 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Medicine University of South Florida Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William V.","family":"Nikolic","sequence":"additional","affiliation":[{"name":"Department of Genetics Faculty of Medicine University of Kragujevac Svetozara Kragujevac Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bengtson","sequence":"additional","affiliation":[{"name":"Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center Department of Psychiatry and Neurosciences All Children's Hospital College of Medicine University of South Florida Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Mori","sequence":"additional","affiliation":[{"name":"Departments of Biomedical Sciences and Pathology Saitama Medical Center and Saitama Medical University Kawagoe Saitama 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