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Pathomechanisms of Paraneoplastic Myasthenia Gravis
Thymic T cell development is characterized by sequential selection processes to ensure generation of a self-tolerant, immuncompetent mature T cell repertoire. Malfunction of any of these selection processes may potentially result in either immunodeficiency or autoimmunity. Myasthenia gravis (MG) is...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2003
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270674/ https://www.ncbi.nlm.nih.gov/pubmed/14575152 http://dx.doi.org/10.1080/10446670310001598528 |
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author | Ströbel, Philipp Preisshofen, Tobias Helmreich, Markus Müller-Hermelink, Hans Konrad Marx, Alexander |
author_facet | Ströbel, Philipp Preisshofen, Tobias Helmreich, Markus Müller-Hermelink, Hans Konrad Marx, Alexander |
author_sort | Ströbel, Philipp |
collection | PubMed |
description | Thymic T cell development is characterized by sequential selection processes to ensure generation of a self-tolerant, immuncompetent mature T cell repertoire. Malfunction of any of these selection processes may potentially result in either immunodeficiency or autoimmunity. Myasthenia gravis (MG) is a typical autoimmune manifestation of thymic epithelial tumors (thymomas) and is related to the capacity of these tumors to generate and export mature T cells. Analysis of the factors that lead to autoimmunization in thymomas will help to understand the mechanisms that prevent MG under physiological conditions in humans. In a comparison of MG(+) and MG(-) thymomas, we could show that only thymomas capable of generating mature CD45RA+CD4+ T cells are associated with MG (p< 0.0001), while terminal thymopoiesis was abrogated in MG(-) thymomas. In particular, acquisition of the CD27+CD45RA+ phenotype appears to be a critical checkpoint of late T cell development in the human thymus and may play an important role in the prevention of autoimmunity. Moreover, MG(-) thymomas were virtually depleted of regulatory (CD4+CD25+) T cells (regT), while regT were readily detectable in MG(+) thymomas, albeit at significantly reduced numbers compared to control thymuses. Thus, in MG(+) thymoma patients, thymectomy apparently also results in removal of a regulatory T cell pool and may explain the frequent temporary postoperative deterioration of MG in these patients. |
format | Text |
id | pubmed-2270674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-22706742008-03-31 Pathomechanisms of Paraneoplastic Myasthenia Gravis Ströbel, Philipp Preisshofen, Tobias Helmreich, Markus Müller-Hermelink, Hans Konrad Marx, Alexander Clin Dev Immunol Research Article Thymic T cell development is characterized by sequential selection processes to ensure generation of a self-tolerant, immuncompetent mature T cell repertoire. Malfunction of any of these selection processes may potentially result in either immunodeficiency or autoimmunity. Myasthenia gravis (MG) is a typical autoimmune manifestation of thymic epithelial tumors (thymomas) and is related to the capacity of these tumors to generate and export mature T cells. Analysis of the factors that lead to autoimmunization in thymomas will help to understand the mechanisms that prevent MG under physiological conditions in humans. In a comparison of MG(+) and MG(-) thymomas, we could show that only thymomas capable of generating mature CD45RA+CD4+ T cells are associated with MG (p< 0.0001), while terminal thymopoiesis was abrogated in MG(-) thymomas. In particular, acquisition of the CD27+CD45RA+ phenotype appears to be a critical checkpoint of late T cell development in the human thymus and may play an important role in the prevention of autoimmunity. Moreover, MG(-) thymomas were virtually depleted of regulatory (CD4+CD25+) T cells (regT), while regT were readily detectable in MG(+) thymomas, albeit at significantly reduced numbers compared to control thymuses. Thus, in MG(+) thymoma patients, thymectomy apparently also results in removal of a regulatory T cell pool and may explain the frequent temporary postoperative deterioration of MG in these patients. Hindawi Publishing Corporation 2003-03 /pmc/articles/PMC2270674/ /pubmed/14575152 http://dx.doi.org/10.1080/10446670310001598528 Text en Copyright © 2003 Hindawi Publishing Corporation. http://creativecommons.org/licenses/by/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Ströbel, Philipp Preisshofen, Tobias Helmreich, Markus Müller-Hermelink, Hans Konrad Marx, Alexander Pathomechanisms of Paraneoplastic Myasthenia Gravis |
title | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
title_full | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
title_fullStr | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
title_full_unstemmed | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
title_short | Pathomechanisms of Paraneoplastic Myasthenia Gravis |
title_sort | pathomechanisms of paraneoplastic myasthenia gravis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270674/ https://www.ncbi.nlm.nih.gov/pubmed/14575152 http://dx.doi.org/10.1080/10446670310001598528 |
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