{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:44:15Z","timestamp":1777509855872,"version":"3.51.4"},"reference-count":51,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"},{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:p>\n                    Hematopoietic chimerism resulting from prenatal marrow transplantation does not consistently result in allotolerance for unidentified causes. In a C57BL\/6-into-FVB\/N murine model, we transplanted T-cell-depleted adult marrow on gestational day 14 to elucidate the immunological significance of chimerism towards postnatal tolerance. Postnatally, chimerism was examined by flow cytometry, and tolerance by skin transplantation and mixed lymphocyte reaction. Regulatory T cells were quantified by FoxP3 expression. Peripheral chimerism linearly related to thymic chimerism, and predicted the degree of graft acceptance with levels &gt;3% at skin placement, yielding consistent skin tolerance. Low- and high-level chimeras had lower intrathymic CD3\n                    <jats:sup>high<\/jats:sup>\n                    expression than microchimeras or untransplanted mice. Regardless of the skin tolerance status in mixed chimeras, donor-specific alloreactivity by lymphocytes was suppressed but could be partially restored by exogenous interleukin-2. Recipients that lost peripheral chimerism did not accept donor skin unless prior donor skin had engrafted at sufficient chimerism levels, suggesting that complete tolerance can develop as a consequence of chimerism-related immunosuppression of host lymphocytes and the tolerogenic effects of donor skin. Thus, hematopoietic chimerism exerted immunomodulatory effects on the induction phase of allograft tolerance. Once established, skin tolerance did not fade away along with spontaneous regression of peripheral and tissue chimerism, as well as removal of engrafted donor skin. Neither did it break following in vivo depletion of increased regulatory T cells, and subcutaneous interleukin-2 injection beneath the engrafted donor skin. Those observations indicate that the maintenance of skin tolerance is multifaceted, neither solely dependent upon hematopoietic chimerism and engrafted donor skin nor on the effects of regulatory T cells or clonal anergy. We conclude that hematopoietic chimerism generated by in utero hematopoietic stem cell transplantation is critical to establish rather than maintain postnatal skin tolerance. Therefore, the diminution of hematopoietic chimerism below a threshold level does not nullify an existing tolerance state, but lessens the chance of enabling complete tolerance.\n                  <\/jats:p>","DOI":"10.3727\/096368910x516583","type":"journal-article","created":{"date-parts":[[2010,12,7]],"date-time":"2010-12-07T10:34:01Z","timestamp":1291718041000},"page":"1609-1622","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Characterization of Tolerance Induction through Prenatal Marrow Transplantation: The Requirement for a Threshold Level of Chimerism to Establish Rather than Maintain Postnatal Skin Tolerance"],"prefix":"10.1177","volume":"19","author":[{"given":"Jeng-Chang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Ling","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang-Shiou","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Yeh","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus O.","family":"Muench","sequence":"additional","affiliation":[{"name":"Blood Systems Research Institute and Department of Laboratory Medicine, University of California, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Rui","family":"Shen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsueh-Ling","family":"Chang","sequence":"additional","affiliation":[{"name":"Pediatric Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu-Yueh","family":"Yu","sequence":"additional","affiliation":[{"name":"Pediatric Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren-Huei","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2010,12,1]]},"reference":[{"key":"bibr1-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116264"},{"key":"bibr2-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979471"},{"key":"bibr3-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1038\/172603a0"},{"key":"bibr4-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1038\/hdy.1952.20"},{"key":"bibr5-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.12.4681.bloodjournal86124681"},{"key":"bibr6-096368910X516583","doi-asserted-by":"publisher","DOI":"10.3727\/096368908785095971"},{"key":"bibr7-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05040.x"},{"key":"bibr8-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1159\/000081367"},{"key":"bibr9-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2007.01570.x"},{"key":"bibr10-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2004.05.003"},{"key":"bibr11-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270406"},{"key":"bibr12-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200102150-00004"},{"key":"bibr13-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.09.029"},{"key":"bibr14-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200004150-00008"},{"key":"bibr15-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199609270-00026"},{"key":"bibr16-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0016"},{"key":"bibr17-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199601150-00010"},{"key":"bibr18-096368910X516583","first-page":"354","volume":"152","author":"Hume D. M.","year":"1960","journal-title":"Ann. Surg."},{"key":"bibr19-096368910X516583","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1444"},{"key":"bibr20-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199501000-00018"},{"key":"bibr21-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199912150-00022"},{"key":"bibr22-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199608150-00014"},{"key":"bibr23-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199709150-00008"},{"key":"bibr24-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1038\/15248"},{"issue":"1","key":"bibr25-096368910X516583","first-page":"443","volume":"13","author":"Koretz S. H.","year":"1981","journal-title":"Transplant. Proc."},{"key":"bibr26-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.08.007"},{"key":"bibr27-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1038\/nri1002"},{"issue":"5","key":"bibr28-096368910X516583","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.4049\/jimmunol.104.5.1236","volume":"104","author":"Lubaroff D. M.","year":"1970","journal-title":"J. Immunol."},{"key":"bibr29-096368910X516583","first-page":"821","volume":"46","author":"Mannick J. A.","year":"1959","journal-title":"Surgery"},{"key":"bibr30-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000067945.90241.F4"},{"key":"bibr31-096368910X516583","first-page":"272","volume":"48","author":"Murray J. E.","year":"1960","journal-title":"Surgery"},{"key":"bibr32-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1126\/science.102.2651.400"},{"key":"bibr33-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199403033300919"},{"key":"bibr34-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(02)00803-2"},{"issue":"3","key":"bibr35-096368910X516583","first-page":"191","volume":"9","author":"Sharabi Y.","year":"1992","journal-title":"Bone Marrow Transplant."},{"key":"bibr36-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-922436"},{"key":"bibr37-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199908270-00006"},{"key":"bibr38-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)91840-5"},{"key":"bibr39-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90054-O"},{"key":"bibr40-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00122-4"},{"issue":"12","key":"bibr41-096368910X516583","doi-asserted-by":"crossref","first-page":"5631","DOI":"10.4049\/jimmunol.155.12.5631","volume":"155","author":"Taniguchi H.","year":"1995","journal-title":"J. Immunol."},{"issue":"3","key":"bibr42-096368910X516583","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.4049\/jimmunol.153.3.1087","volume":"153","author":"Tomita Y.","year":"1994","journal-title":"J. Immunol."},{"key":"bibr43-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200001150-00006"},{"key":"bibr44-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200204270-00023"},{"key":"bibr45-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199908270-00001"},{"key":"bibr46-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(96)10069-4"},{"key":"bibr47-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1038\/nri1027"},{"key":"bibr48-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2007.01839.x"},{"key":"bibr49-096368910X516583","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.8.5258"},{"key":"bibr50-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1038\/ni1394"},{"key":"bibr51-096368910X516583","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7401138"}],"container-title":["Cell Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.3727\/096368910X516583","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.3727\/096368910X516583","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.3727\/096368910X516583","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:35:50Z","timestamp":1777390550000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.sagepub.com\/doi\/10.3727\/096368910X516583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12]]},"references-count":51,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["10.3727\/096368910X516583"],"URL":"https:\/\/doi.org\/10.3727\/096368910x516583","relation":{},"ISSN":["0963-6897","1555-3892"],"issn-type":[{"value":"0963-6897","type":"print"},{"value":"1555-3892","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12]]}}}