Clonal expansions of CD4+ B helper T cells in autoimmune myasthenia gravis
| Autor: | Jens Kruth, Bernhard Hemmer, Wolfgang H. Oertel, Nicholas Willcox, Björn Tackenberg, Norbert Sommer, Kerstin Schlegel, Johanna E. Bartholomaeus |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Adolescent T cell Immunology Molecular Sequence Data Immunoglobulin Variable Region chemical and pharmacologic phenomena Biology medicine.disease_cause Epitope Autoimmunity Antigen Myasthenia Gravis medicine Immunology and Allergy Humans Amino Acid Sequence Aged Cell Proliferation Aged 80 and over T-cell receptor Autoantibody hemic and immune systems T helper cell T-Lymphocytes Helper-Inducer Middle Aged medicine.disease Virology Myasthenia gravis Clone Cells medicine.anatomical_structure Genes T-Cell Receptor beta Female |
| Zdroj: | European journal of immunology. 37(3) |
| ISSN: | 0014-2980 |
| Popis: | The weakness in myasthenia gravis (MG) is mediated by T helper cell (Th)-dependent autoantibodies against neuromuscular epitopes. So far, analyzing Th phenotypes or antigen specificities has yielded very few clues to pathogenesis. Here we adopt an alternative antigen-independent approach, analyzing T cell receptor (TCR) Vbeta usage/expansions in blood from 118 MG patients. We found major expansions (or= five standard deviations above the mean of 118 healthy, individually age- and sex-matched controls) in diverse Vbeta in 21 patients (17.6%, p0.001) among CD4+ T cells, and in 45 patients (38.1%, p0.001) among CD8+ T cells. In informative probands, the expanded CD4+ cells consistently showed a Th cell phenotype (CD57+CXCR5+) and expressed Th1 cytokines. Furthermore, their expression of markers for activation, lymphocyte trafficking and B cell-activating ability persisted foror=3 years. Surprisingly, we noted a selective decline in the expansions/their CD57 positivity while the probands' MG was improving. CDR3 spectratyping suggested mono- or oligoclonal origins, which were confirmed by the prevalent TCR Vbeta CDR3 sequences of Th cells cloned from repeat bleeds. Thus, our data provide evidence for persistent clonally expanded CD4+ B helper T cell populations in the blood of MG patients. These unexpected CD4+ expansions might hold valuable clues to MG immunopathogenesis. |
| Databáze: | OpenAIRE |
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