A pathogenetic role for the thymoma in myasthenia gravis. Autosensitization of IL-4- producing T cell clones recognizing extracellular acetylcholine receptor epitopes presented by minority class II isotypes
| Autor: | Nick Willcox, David Beeson, Ioannis Roxanis, Moss P, John Curnow, N Pantic, N Nagvekar, A Vincent, John Newsom-Davis, A M Moody |
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| Rok vydání: | 1998 |
| Předmět: |
Thymoma
T cell Molecular Sequence Data Receptors Antigen T-Cell Antigen-Presenting Cells Autoimmunity Biology Epitope Interferon-gamma Antigens CD Myasthenia Gravis medicine Humans Receptors Cholinergic Amino Acid Sequence Antigen-presenting cell Interleukin 4 Histocompatibility Antigens Class II General Medicine Sequence Analysis DNA T-Lymphocytes Helper-Inducer medicine.disease Flow Cytometry Molecular biology Immunohistochemistry Myasthenia gravis Clone Cells Epitope mapping medicine.anatomical_structure Interleukin-4 Alpha chain Epitope Mapping Research Article |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0021-9738 |
| Popis: | Myasthenia gravis (MG) is caused by helper T cell-dependent autoantibodies against the muscle acetylcholine receptor (AChR). Thymic epithelial tumors (thymomas) occur in 10% of MG patients, but their autoimmunizing potential is unclear. They express mRNAs encoding AChR alpha and epsilon subunits, and might aberrantly select or sensitize developing thymocytes or recirculating peripheral T cells against AChR epitopes. Alternatively, there could be defective self-tolerance induction in the abundant maturing thymocytes that they usually generate. For the first time, we have isolated and characterized AChR-specific T cell clones from two MG thymomas. They recognize extracellular epitopes (alpha75-90 and alpha149-158) which are processed very efficiently from muscle AChR. Both clones express CD4 and CD8alpha, and have a Th-0 cytokine profile, producing IL-4 as well as IFN-gamma. They are restricted to HLA-DP14 and DR52a; expression of these minority isotypes was strong on professional antigen-presenting cells in the donors' tumors, although it is generally weak in the periphery. The two clones' T cell receptor beta chains are different, but their alpha chain sequences are very similar. These resemblances, and the striking contrasts with T cells previously cloned from non-thymoma patients, show that thymomas generate and actively induce specific T cells rather than merely failing to tolerize them against self antigens. |
| Databáze: | OpenAIRE |
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