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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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2005-07, Vol.65 (14), p.6443-6449
Main Authors: BOS, Rinke, VAN DUIKEREN, Suzanne, VAN HALL, Thorbald, KAAIJK, Patricia, TAUBERT, Richard, KYEWSKI, Bruno, KLEIN, Ludger, MELIEF, Cornelis J. M, OFFRINGA, Rienk
Format: Article
Language:English
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
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-05-0666