{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:22:39Z","timestamp":1790965359841,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2003,3,1]],"date-time":"2003-03-01T00:00:00Z","timestamp":1046476800000},"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":[[2003,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>High level expression of Fc\u03b5RI\u03b3 chain replaces the deficient TCR \u03b6-chain and contributes to altered TCR\/CD3-mediated signaling abnormalities in T cells of patients with systemic lupus erythematosus. Increased responsiveness to Ag has been considered to lead to autoimmunity. To test this concept, we studied early signaling events and IL-2 production in fresh cells transfected with a eukaryotic expression vector encoding the Fc\u03b5RI\u03b3 gene. We found that the overexpressed Fc\u03b5RI\u03b3 chain colocalizes with the CD3\u03b5 chain on the surface membrane of T cells and that cross-linking of the new TCR\/CD3 complex leads to a dramatic increase of intracytoplasmic calcium concentration, protein tyrosine phosphorylation, and IL-2 production. We observed that overexpression of Fc\u03b5RI\u03b3 is associated with increased phosphorylation of Syk kinase, while the endogenous TCR \u03b6-chain is down-regulated. We propose that altered composition of the CD3 complex leads to increased T cell responsiveness to TCR\/CD3 stimulation and sets the biochemical grounds for the development of autoimmunity.<\/jats:p>","DOI":"10.4049\/jimmunol.170.6.2871","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:21:23Z","timestamp":1398036083000},"page":"2871-2876","source":"Crossref","is-referenced-by-count":33,"title":["Forced Expression of the Fc Receptor \u03b3-Chain Renders Human T Cells Hyperresponsive to TCR\/CD3 Stimulation"],"prefix":"10.1093","volume":"170","author":[{"given":"Madhusoodana P","family":"Nambiar","sequence":"first","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"},{"name":"Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn U","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos G","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal G","family":"Warke","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George C","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"},{"name":"Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,3,15]]},"reference":[{"key":"2026020210120361600_R1","first-page":"B24","volume-title":"Nature","year":"1999"},{"key":"2026020210120361600_R2","first-page":"20","volume-title":"Allergy","year":"1995"},{"key":"2026020210120361600_R3","first-page":"55","volume-title":"Clin. Immunol.","year":"1999"},{"key":"2026020210120361600_R4","first-page":"272","volume-title":"Mol. Cell Biol.","year":"1995"},{"key":"2026020210120361600_R5","first-page":"29697","volume-title":"J. Biol. Chem.","year":"1994"},{"key":"2026020210120361600_R6","first-page":"388","volume-title":"Blood","year":"1997"},{"key":"2026020210120361600_R7","first-page":"2563","volume-title":"J. Immunol.","year":"1992"},{"key":"2026020210120361600_R8","first-page":"690","volume-title":"Curr. Opin. Immunol.","year":"1998"},{"key":"2026020210120361600_R9","first-page":"203","volume-title":"J. Exp. Med.","year":"1992"},{"key":"2026020210120361600_R10","first-page":"4347","volume-title":"EMBO J.","year":"1993"},{"key":"2026020210120361600_R11","first-page":"1795","volume-title":"Science","year":"1992"},{"key":"2026020210120361600_R12","first-page":"1327","volume-title":"Clin. Cancer Res.","year":"1995"},{"key":"2026020210120361600_R13","first-page":"2320","volume-title":"J. Immunol.","year":"1996"},{"key":"2026020210120361600_R14","first-page":"222","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020210120361600_R15","first-page":"11875","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1993"},{"key":"2026020210120361600_R16","first-page":"1114","volume-title":"Arthritis Rheum.","year":"2001"},{"key":"2026020210120361600_R17","first-page":"2269","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020210120361600_R18","first-page":"305","volume-title":"Clin. Immunol. Immunopathol.","year":"1998"},{"key":"2026020210120361600_R19","first-page":"1448","volume-title":"J. Clin. Invest.","year":"1998"},{"key":"2026020210120361600_R20","first-page":"5287","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020210120361600_R21","first-page":"329","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026020210120361600_R22","first-page":"145","volume-title":"Clin. Immunol.","year":"2002"},{"key":"2026020210120361600_R23","first-page":"9709","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1988"},{"key":"2026020210120361600_R24","first-page":"163","volume-title":"Arthritis Rheum.","year":"2002"},{"key":"2026020210120361600_R25","first-page":"1859","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026020210120361600_R26","first-page":"1336","volume-title":"Arthritis Rheum.","year":"2001"},{"key":"2026020210120361600_R27","first-page":"10498","volume-title":"J. Biol. Chem.","year":"1995"},{"key":"2026020210120361600_R28","first-page":"2549","volume-title":"J. Clin. Invest.","year":"1996"},{"key":"2026020210120361600_R29","first-page":"72","volume-title":"Clin. Exp. Immunol.","year":"1996"},{"key":"2026020210120361600_R30","first-page":"3914","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020210120361600_R31","first-page":"8","volume-title":"Clin. Immunol. Immunopathol.","year":"1993"},{"key":"2026020210120361600_R32","first-page":"81","volume-title":"Nature","year":"1996"},{"key":"2026020210120361600_R33","first-page":"4216","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210120361600_R34","first-page":"4147","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210120361600_R35","first-page":"443","volume-title":"Trends Immunol.","year":"2001"},{"key":"2026020210120361600_R36","first-page":"147","volume-title":"Nat. Rev. Immunol.","year":"2001"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/6\/2871\/62569964\/2871.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/6\/2871\/62569964\/2871.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:15:34Z","timestamp":1770045334000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/170\/6\/2871\/8028578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2003,3,15]]},"published-print":{"date-parts":[[2003,3,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.170.6.2871","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,3]]},"published":{"date-parts":[[2003,3]]}}}