{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:03:43Z","timestamp":1790906623746,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,12,26]]},"abstract":"<jats:p>\n                    Although human embryonic stem (ES) cells may one day provide a renewable source of tissues for cell replacement therapy (CRT), histoincompatibility remains a significant barrier to their clinical application. Current estimates suggest that surprisingly few cell lines may be required to facilitate rudimentary tissue matching. Nevertheless, the degree of disparity between donor and recipient that may prove acceptable, and the extent of matching that is therefore required, remain unknown. To address this issue using a mouse model of CRT, we have derived a panel of ES cell lines that differ from CBA\/Ca recipients at defined genetic loci. Here, we show that even expression of minor histocompatibility (mH) antigens is sufficient to provoke acute rejection of tissues differentiated from ES cells. Nevertheless, despite their immunogenicity\n                    <jats:italic>in vivo<\/jats:italic>\n                    , transplantation tolerance may be readily established by using minimal host conditioning with nondepleting monoclonal antibodies specific for the T cell coreceptors, CD4 and CD8. This propensity for tolerance could be attributed to the paucity of professional antigen-presenting cells and the expression of transforming growth factor (TGF)-\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    . Together, these factors contribute to a state of acquired immune privilege that favors the polarization of infiltrating T cells toward a regulatory phenotype. Although the natural privileged status of ES cell-derived tissues is, therefore, insufficient to overcome even mH barriers, our findings suggest it may be harnessed effectively for the induction of dominant tolerance with minimal therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0710265105","type":"journal-article","created":{"date-parts":[[2007,12,18]],"date-time":"2007-12-18T23:09:15Z","timestamp":1198019355000},"page":"20920-20925","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":150,"title":["Embryonic stem cell-derived tissues are immunogenic but their inherent immune privilege promotes the induction of tolerance"],"prefix":"10.1073","volume":"104","author":[{"given":"Nathan J.","family":"Robertson","sequence":"first","affiliation":[{"name":"*Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances A.","family":"Brook","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Cobbold","sequence":"additional","affiliation":[{"name":"*Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Waldmann","sequence":"additional","affiliation":[{"name":"*Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Fairchild","sequence":"additional","affiliation":[{"name":"*Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,12,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1145"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1014"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1041"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21137"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.07.005"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.07.010"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67813-0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.142298299"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.22-4-448"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2006.15.707"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0188"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2005.03.049"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.525824"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5709"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/4.1.59"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2002.19007.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830201231"},{"key":"e_1_3_3_18_2","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.4049\/jimmunol.163.9.4805","article-title":"CD40 ligand blockade induces CD4+ T cell tolerance and linked suppression","volume":"163","author":"Honey K","year":"1999","unstructured":"K Honey, SP Cobbold, H Waldmann, CD40 ligand blockade induces CD4+ T cell tolerance and linked suppression. J Immunol 163, 4805\u20134810 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400084101"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/9783527619696.ch47"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1668"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.12.5809"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1224"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041560205"},{"key":"e_1_3_3_25_2","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.4049\/jimmunol.161.4.1868","article-title":"Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: No requirement for CD8+ T cells or B cells","volume":"161","author":"Zelenika D","year":"1998","unstructured":"D Zelenika, et al., Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: No requirement for CD8+ T cells or B cells. J Immunol 161, 1868\u20131874 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00120-0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6003"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.1991"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.1.178"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/172603a0"},{"key":"e_1_3_3_31_2","first-page":"347","volume-title":"Immunological Tolerance: Methods and Protocols","author":"Robertson NJ","year":"2007","unstructured":"NJ Robertson, PJ Fairchild, H Waldmann Immunological Tolerance: Methods and Protocols, ed PJ Fairchild (Humana Press, Totowa, NJ), pp. 347\u2013353 (2007)."},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2201"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0710265105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T05:56:06Z","timestamp":1684130166000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0710265105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12,26]]},"references-count":32,"journal-issue":{"issue":"52","published-print":{"date-parts":[[2007,12,26]]}},"alternative-id":["10.1073\/pnas.0710265105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0710265105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12,26]]},"assertion":[{"value":"2007-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}