Impairment of regulatory T cells in myasthenia gravis: Studies in an experimental model

Smadar Gertel-Lapter, Keren Mizrachi, Sonia Berrih-Aknin, Sara Fuchs, Miriam C. Souroujon

Research output: Contribution to journalReview articlepeer-review


Myasthenia gravis (MG) is an antibody mediated, T cell dependent autoimmune disease characterized by muscle fatigability in which autoantibodies directed to the acetylcholine receptor (AChR) impair neuromuscular transmission. The identification of CD4+CD25+Foxp3+ Treg cells as important regulators of tolerance opened a major area of investigation raising the possibility that a dysfunction in the Treg compartment is involved in the etiology and pathogenesis of autoimmune diseases, including MG. In this paper we summarize shortly Treg abnormalities that were reported in MG patients and report on our studies of Treg in experimental autoimmune MG (EAMG). Hopefully these studies would pave the way towards the development of novel Treg-based treatment modalities that will restore self-tolerance in MG and other autoimmune diseases.In our previous studies in EAMG we have shown that Treg cells transferred from healthy rat donors to myasthenic rats suppress EAMG. However, Treg cells from sick animals do not have the same in vivo suppressive activity as those from healthy donors. The objective of the present study was to further characterize quantitative and qualitative alterations in Treg cells of rats with EAMG. We found that the frequency of CD4+CD25+Foxp3+ Treg cells within the spleen and PBL was decreased in EAMG rats as compared to naïve and CFA-immunized healthy controls. Treg cells from myasthenic rats were less effective than Treg cells from controls in suppressing the proliferation of CD4+ T effector cells in response to ConA and of B cells in response to LPS. Moreover, CD4+CD25+ cells from EAMG rats exhibited an elevated extent of apoptosis and expressed upregulated levels of FAS and of Th17-associated cytokines. Since EAMG is an induced disease, these quantitative and qualitative alterations in Treg cells do not reflect predisposing impairments and seem to be associated with the specific autoimmune response resulting from AChR immunization.

Original languageEnglish
Pages (from-to)894-903
Number of pages10
JournalAutoimmunity Reviews
Issue number9
StatePublished - Jul 2013

Bibliographical note

Funding Information:
Studies from our lab described in the paper were supported by grants from the European Commission (FIGHT-MG, contract # FP7 HEALTH-2009-242-210 ), the Muscular Dystrophy Association of America (MDA) , the Association Francaise Contre les Myopathies (AFM) , and the Open University of Israel's Research Fund .

Copyright 2014 Elsevier B.V., All rights reserved.


  • EAMG
  • Myasthenia gravis
  • Regulatory T cells


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