Expression of a natural tumor antigen by thymic epithelial cells impairs the tumor-protective CD4+ T-cell repertoire
A variety of antigens that display a highly tissue-specific expression pattern have recently found to be also expressed in medullary thymic epithelial cells (mTEC). This unique feature of mTEC plays an important role in preventing hazardous autoimmune responses through thymic tolerization of T-cell...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2005-07, Vol.65 (14), p.6443-6449 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | BOS, Rinke VAN DUIKEREN, Suzanne VAN HALL, Thorbald KAAIJK, Patricia TAUBERT, Richard KYEWSKI, Bruno KLEIN, Ludger MELIEF, Cornelis J. M OFFRINGA, Rienk |
| description | A variety of antigens that display a highly tissue-specific expression pattern have recently found to be also expressed in medullary thymic epithelial cells (mTEC). This unique feature of mTEC plays an important role in preventing hazardous autoimmune responses through thymic tolerization of T-cell subsets directed against autoantigens but could also limit the possibility of exploiting tumor-associated antigens for immune-mediated targeting of cancers. Our present study shows that expression of carcinoembryonic antigen (CEA) in thymic epithelial cells of CEA-transgenic mice results in tolerization of a major fraction of the CD4+ T-cell repertoire against this antigen, thereby markedly limiting the effect of CEA-specific immunization against CEA-overexpressing tumors. The expression of CEA in mTEC of CEA-transgenic mice is mirrored by its expression in human mTEC, arguing that promiscuous gene expression in these thymic stromal cells needs to be considered as a potential hurdle for immunotherapies of cancer that target tissue-specific autoantigens. |
| doi_str_mv | 10.1158/0008-5472.CAN-05-0666 |
| format | Article |
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Our present study shows that expression of carcinoembryonic antigen (CEA) in thymic epithelial cells of CEA-transgenic mice results in tolerization of a major fraction of the CD4+ T-cell repertoire against this antigen, thereby markedly limiting the effect of CEA-specific immunization against CEA-overexpressing tumors. The expression of CEA in mTEC of CEA-transgenic mice is mirrored by its expression in human mTEC, arguing that promiscuous gene expression in these thymic stromal cells needs to be considered as a potential hurdle for immunotherapies of cancer that target tissue-specific autoantigens.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-05-0666</identifier><identifier>PMID: 16024649</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Amino Acid Sequence ; Animals ; Antineoplastic agents ; Biological and medical sciences ; Carcinoembryonic Antigen - biosynthesis ; Carcinoembryonic Antigen - genetics ; Carcinoembryonic Antigen - immunology ; CD4-Positive T-Lymphocytes - immunology ; Epithelial Cells - immunology ; Epitopes ; Lymphocyte Activation ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular Sequence Data ; Peptide Fragments - immunology ; Pharmacology. Drug treatments ; Thymus Gland - immunology ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 2005-07, Vol.65 (14), p.6443-6449</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-5f4178082f7ac8c6b9020af949e3b3b2384cb7e386e35e83393646c5ee299dcf3</citedby><cites>FETCH-LOGICAL-c402t-5f4178082f7ac8c6b9020af949e3b3b2384cb7e386e35e83393646c5ee299dcf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16960974$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16024649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BOS, Rinke</creatorcontrib><creatorcontrib>VAN DUIKEREN, Suzanne</creatorcontrib><creatorcontrib>VAN HALL, Thorbald</creatorcontrib><creatorcontrib>KAAIJK, Patricia</creatorcontrib><creatorcontrib>TAUBERT, Richard</creatorcontrib><creatorcontrib>KYEWSKI, Bruno</creatorcontrib><creatorcontrib>KLEIN, Ludger</creatorcontrib><creatorcontrib>MELIEF, Cornelis J. M</creatorcontrib><creatorcontrib>OFFRINGA, Rienk</creatorcontrib><title>Expression of a natural tumor antigen by thymic epithelial cells impairs the tumor-protective CD4+ T-cell repertoire</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>A variety of antigens that display a highly tissue-specific expression pattern have recently found to be also expressed in medullary thymic epithelial cells (mTEC). This unique feature of mTEC plays an important role in preventing hazardous autoimmune responses through thymic tolerization of T-cell subsets directed against autoantigens but could also limit the possibility of exploiting tumor-associated antigens for immune-mediated targeting of cancers. Our present study shows that expression of carcinoembryonic antigen (CEA) in thymic epithelial cells of CEA-transgenic mice results in tolerization of a major fraction of the CD4+ T-cell repertoire against this antigen, thereby markedly limiting the effect of CEA-specific immunization against CEA-overexpressing tumors. The expression of CEA in mTEC of CEA-transgenic mice is mirrored by its expression in human mTEC, arguing that promiscuous gene expression in these thymic stromal cells needs to be considered as a potential hurdle for immunotherapies of cancer that target tissue-specific autoantigens.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Carcinoembryonic Antigen - biosynthesis</subject><subject>Carcinoembryonic Antigen - genetics</subject><subject>Carcinoembryonic Antigen - immunology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Epithelial Cells - immunology</subject><subject>Epitopes</subject><subject>Lymphocyte Activation</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Peptide Fragments - immunology</subject><subject>Pharmacology. 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Drug treatments</topic><topic>Thymus Gland - immunology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BOS, Rinke</creatorcontrib><creatorcontrib>VAN DUIKEREN, Suzanne</creatorcontrib><creatorcontrib>VAN HALL, Thorbald</creatorcontrib><creatorcontrib>KAAIJK, Patricia</creatorcontrib><creatorcontrib>TAUBERT, Richard</creatorcontrib><creatorcontrib>KYEWSKI, Bruno</creatorcontrib><creatorcontrib>KLEIN, Ludger</creatorcontrib><creatorcontrib>MELIEF, Cornelis J. 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Our present study shows that expression of carcinoembryonic antigen (CEA) in thymic epithelial cells of CEA-transgenic mice results in tolerization of a major fraction of the CD4+ T-cell repertoire against this antigen, thereby markedly limiting the effect of CEA-specific immunization against CEA-overexpressing tumors. The expression of CEA in mTEC of CEA-transgenic mice is mirrored by its expression in human mTEC, arguing that promiscuous gene expression in these thymic stromal cells needs to be considered as a potential hurdle for immunotherapies of cancer that target tissue-specific autoantigens.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16024649</pmid><doi>10.1158/0008-5472.CAN-05-0666</doi><tpages>7</tpages></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 2005-07, Vol.65 (14), p.6443-6449 |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Amino Acid Sequence Animals Antineoplastic agents Biological and medical sciences Carcinoembryonic Antigen - biosynthesis Carcinoembryonic Antigen - genetics Carcinoembryonic Antigen - immunology CD4-Positive T-Lymphocytes - immunology Epithelial Cells - immunology Epitopes Lymphocyte Activation Medical sciences Mice Mice, Inbred C57BL Mice, Transgenic Molecular Sequence Data Peptide Fragments - immunology Pharmacology. Drug treatments Thymus Gland - immunology Tumors |
| title | Expression of a natural tumor antigen by thymic epithelial cells impairs the tumor-protective CD4+ T-cell repertoire |
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