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+ T cells developing in a thymus that lacks MHC molecules on hemopoietic cells display no autoreactivity in vivo upon transfer into syngeneic wild-type mice, implying tolerance induction by nonhemopoietic cells - that is, by epithelial cells. These results emphasize a certain degree of redundancy in the contribution of different stromal cells to the tolerance process.
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CD4 T cell tolerance to human C-reactive protein, an inducible serum protein, is mediated by medullary thymic epithelium
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This study shows that self-tolerance to proteolipid protein (PLP), a major myelin antigen, is mediated by central tolerance via ectopic expression of PLP in thymic epithelial cells. Because of exclusive expression of a shorter splice form of PLP in the thymus, self-tolerance to the full-length protein is incomplete - thus predisposing to autoimmunity.
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67
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An acetylcholine receptor alpha subunit promoter confers intrathymic expression in transgenic mice. Implications for tolerance of a transgenic self-antigen and for autoreactivity in myasthenia gravis
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This thorough study shows that the promotor of the muscle-specific α-subunit of the acetylcholine receptor confers specific expression of the β-galactosidase gene to thymic epithelial cells, resulting in specific tolerance. Interestingly, expression in epithelial cells was only observed with the longer of two promotor constructs - suggesting specific regulation of this promotor in trans by thymic epithelial cells. Again this study emphasizes the role of ectopic expression of tissue-specific genes in thymic stromal cells and its role in tolerance induction and autoimmunity.
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Salmon A.M., Bruand C., Cardona A., Changeux J.P., Berrih-Aknin S. An acetylcholine receptor alpha subunit promoter confers intrathymic expression in transgenic mice. Implications for tolerance of a transgenic self-antigen and for autoreactivity in myasthenia gravis. J Clin Invest. 101:1998;2340-2350. This thorough study shows that the promotor of the muscle-specific α-subunit of the acetylcholine receptor confers specific expression of the β-galactosidase gene to thymic epithelial cells, resulting in specific tolerance. Interestingly, expression in epithelial cells was only observed with the longer of two promotor constructs - suggesting specific regulation of this promotor in trans by thymic epithelial cells. Again this study emphasizes the role of ectopic expression of tissue-specific genes in thymic stromal cells and its role in tolerance induction and autoimmunity.
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Viret C., Barlow A.K., Janeway C.A. Jr. On the intrathymic intercellular transfer of self-determinants. Immunol Today. 20:1999;8-10. This paper discusses the concept of intercelluar self-antigen transfer ('antigen spreading') within the thymus as a means to increase the likelihood of antigen encounter by rare autoreactive thymocytes.
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Self major histocompatibility complex class I antigens expressed solely in lymphoid cells do not induce tolerance in the CD4+ T cell compartment
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+ regulatory T cells that are generated in the thymus and that are able to control autoreactive T cells in vivo. The exact genesis and selection of these regulatory T cells remains unclear; mEpcs expressing tissue-specific antigens may be critically involved in these events.
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+ regulatory T cells that are generated in the thymus and that are able to control autoreactive T cells in vivo. The exact genesis and selection of these regulatory T cells remains unclear; mEpcs expressing tissue-specific antigens may be critically involved in these events.
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