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- Dokumenttyp:
- Journal Article; Research Support, Non-U.S. Gov't
- Autor(en):
- Tackenberg, B; Kruth, J; Bartholomaeus, JE; Schlegel, K; Oertel, WH; Willcox, N; Hemmer, B; Sommer, N
- Titel:
- Clonal expansions of CD4+ B helper T cells in autoimmune myasthenia gravis.
- Abstract:
- 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%, p<0.001) among CD4+ T cells, and in 45 patients (38.1%, p<0.001) 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 for >or=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.
- Zeitschriftentitel:
- Eur J Immunol
- Jahr:
- 2007
- Band / Volume:
- 37
- Heft / Issue:
- 3
- Seitenangaben Beitrag:
- 849-63
- Sprache:
- eng
- Volltext / DOI:
- doi:10.1002/eji.200636449
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/17323412
- Print-ISSN:
- 0014-2980
- TUM Einrichtung:
- Neurologische Klinik und Poliklinik
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