title: Expression of a natural tumor antigen by thymic epithelial cells impairs the tumor-protective CD4+ T-cell repertoire.
abstract: 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.
authors: Department of Immunohematology and Blood Transfusion, Tumor Immunology Group, Leiden University Medical Center, Leiden, Netherlands.
authors: Rinke
authors: R
authors: Bos
authors: Suzanne
authors: S
authors: van Duikeren
authors: Thorbald
authors: T
authors: van Hall
authors: Patricia
authors: P
authors: Kaaijk
authors: Richard
authors: R
authors: Taubert
authors: Bruno
authors: B
authors: Kyewski
authors: Ludger
authors: L
authors: Klein
authors: Cornelis J M
authors: CJ
authors: Melief
authors: Rienk
authors: R
authors: Offringa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D000939:Epitopes; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D002272:Carcinoembryonic Antigen; D000939:Epitopes; D010446:Peptide Fragments