{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T02:26:19Z","timestamp":1769653579127,"version":"3.49.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"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":[[2007,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary biliary cirrhosis is characterized by autoreactive T cells specific for the mitochondrial Ag PDC-E2163\u2013176. We studied the ability of eight T cell clones (TCC) specific for PDC-E2163\u2013176 to proliferate or become anergic in the presence of costimulation signals. TCC were stimulated with either human PDC-E2163\u2013176, an Escherichia coli 2-oxoglutarate dehydrogenase mimic (OGDC-E234\u201347), or analogs with amino acid substitutions using HLA-matched allogeneic PBMC or mouse L-DR53 fibroblasts as APC. Based on their differential responses to these peptides (human PDC-E2163\u2013176, E. coli OGDC-E234\u201347) in the different APC systems, TCC were classified as costimulation dependent or independent. Only costimulation-dependent TCC could become anergic. TCC with costimulation-dependent responses to OGDC-E2 become anergic to PDC-E2 when preincubated with mimic, even if costimulation is independent for PDC-E2163\u2013176. Anergic TCC produced IL-10. One selected TCC could not become anergic after preincubation with PDC-E2163\u2013176-pulsed L-DR53 but became anergic using L-DR53 pulsed with PDC-E2 peptide analogs with a substitution at a critical TCR binding site. TCC that only respond to peptide-pulsed PBMC, but not L-DR53, proliferate with peptide-pulsed CD80\/CD86-transfected L-DR53; however, anergy was not induced with peptide-pulsed L-DR53 transfected with only CD80 or CD86. These data highlight that costimulation plays a dominant role in maintaining peripheral tolerance to PBC-specific Ags. They further suggest that, under specific circumstances, molecular mimicry of an autoantigen may restore rather than break peripheral tolerance.<\/jats:p>","DOI":"10.4049\/jimmunol.179.5.3315","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:46Z","timestamp":1397848666000},"page":"3315-3324","source":"Crossref","is-referenced-by-count":9,"title":["Peripheral Tolerance and the Qualitative Characteristics of Autoreactive T Cell Clones in Primary Biliary Cirrhosis"],"prefix":"10.1093","volume":"179","author":[{"given":"Akira","family":"Kawano","sequence":"first","affiliation":[{"name":"Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kamihira","sequence":"additional","affiliation":[{"name":"Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiko","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka ,","place":["Japan"]},{"name":"Research Unit for Human Disease Model, RIKEN Center for Allergy and Immunology , Yokohama ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Niiro","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Medicine, Kyushu University Hospital , Fukuoka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Soejima","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences , Fukuoka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akinobu","family":"Taketomi","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences , Fukuoka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiko","family":"Maehara","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences , Fukuoka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Nakamura","sequence":"additional","affiliation":[{"name":"National Nagasaki Medical Center , Omura ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsumasa","family":"Komori","sequence":"additional","affiliation":[{"name":"National Nagasaki Medical Center , Omura ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Migita","sequence":"additional","affiliation":[{"name":"National Nagasaki Medical Center , Omura ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"National Nagasaki Medical Center , Omura ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuki","family":"Azuma","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Tokyo Medical and Dental University , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Eric","family":"Gershwin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California , Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mine","family":"Harada","sequence":"additional","affiliation":[{"name":"Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,9,1]]},"reference":[{"key":"2026012809311321600_R1","first-page":"1261","volume-title":"N. 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