{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:54:19Z","timestamp":1787727259273,"version":"build-2784847793"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,3,1]]},"abstract":"<jats:p>Spontaneous inflammatory bowel disease (IBD) resembling human ulcerative colitis develops in mice mutant for the T cell receptor alpha gene (TCR-alpha-\/-). TCR-alpha-\/- mice lack TCR-alpha\/beta+ cells but contain TCR-gamma\/delta+ cells and a small population of a unique CD4+, TCR-alpha-\/beta+(low) cells. Since all the immunoglobulin (Ig) classes are present in these mice, help to B cells must be provided by cells other than TCR-alpha\/beta+ cells. In the present study, we found serum levels of IgG1 and IgG2 to be markedly increased in TCR-alpha-\/- mice with IBD as compared to TCR-alpha-\/- mice without IBD or TCR-alpha+\/- controls. An increase in IgG1-, IgG2a- and IgA- but not IgM-secreting mesenteric lymph node (MLN) B cells was detected in TCR-alpha-\/- mutant mice. There was also a marked increase in MLN B cells secreting autoantibody (IgG) to tropomyosin, a cytoskeletal protein. Examination of the hyperplastic MLN showed a marked increase in the number of B, TCR-delta+, and CD4+ TCR-alpha-\/beta+ cells, similar to the cell population observed at the site of colonic inflammation. Analysis of spontaneous cytokine production by MLN cells using an enzyme-linked immunospot assay, immunohistochemistry, and reverse transcription\/polymerase chain reaction showed a decrease of interleukin 2 (IL-2) but a marked increase of IL-4 and interferon gamma (IFN-gamma) production in TCR-alpha-\/- mice with IBD as compared to TCR-alpha-\/- mice without IBD and TCR alpha+\/- control mice. Both TCR-alpha-\/beta+ and TCR-delta+ cells were found to be capable of producing IL-4; IFN-gamma was produced mostly by non-T cells, many of which were shown to be CD3- NK 1.1+ cells. We propose that the cytokine imbalance present in these mice results in expansion of B cells, production and switching of autoantibodies to IgG2 subclass, and development of IBD. It is possible that the unusual CD4+ TCR-alpha-\/beta+ population and expanded TCR-gamma\/delta+ population present in TCR-alpha-\/- mice plays a central role in this abnormal immune response.<\/jats:p>","DOI":"10.1084\/jem.183.3.847","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"847-856","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":179,"title":["Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease."],"prefix":"10.1084","volume":"183","author":[{"given":"A","family":"Mizoguchi","sequence":"first","affiliation":[{"name":"Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Chiba","sequence":"additional","affiliation":[{"name":"Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G M","family":"Spiekermann","sequence":"additional","affiliation":[{"name":"Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Tonegawa","sequence":"additional","affiliation":[{"name":"Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Nagler-Anderson","sequence":"additional","affiliation":[{"name":"Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A K","family":"Bhan","sequence":"additional","affiliation":[{"name":"Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1996,3,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/3\/847\/1678206\/847.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/3\/847\/1678206\/847.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T07:08:20Z","timestamp":1690268900000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/183\/3\/847\/47831\/Cytokine-imbalance-and-autoantibody-production-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1996,3,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.183.3.847","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,3,1]]}}}