The search for the target antigens of multiple sclerosis, part 1: autoreactive CD4+ T lymphocytes as pathogenic effectors and therapeutic targets

@article{Hohlfeld2016TheSF,
  title={The search for the target antigens of multiple sclerosis, part 1: autoreactive CD4+ T lymphocytes as pathogenic effectors and therapeutic targets},
  author={Reinhard Hohlfeld and Klaus Dornmair and Edgar Meinl and Hartmut Wekerle},
  journal={The Lancet Neurology},
  year={2016},
  volume={15},
  pages={198-209}
}
Identification of the target antigens of pathogenic antibodies and T cells is of fundamental importance for understanding the pathogenesis of multiple sclerosis, and for the development of personalised treatments for the disease. Myelin-specific CD4+ T cells emerged long ago as a key player in animal models of multiple sclerosis. Taking a forward-translational approach, autoreactive CD4+ T cells have been studied extensively in patients with multiple sclerosis, and there is evidence, but as yet… Expand
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References

SHOWING 1-10 OF 112 REFERENCES
The search for the target antigens of multiple sclerosis, part 2: CD8+ T cells, B cells, and antibodies in the focus of reverse-translational research
TLDR
New methods allow the reconstruction of human TCRs and antibodies from tissue-infiltrating immune cells, which can be used for the unbiased screening of antigen libraries, and findings from human T-cell receptor (TCR) and B-cell receptors (BCR) repertoire studies provided strong evidence for antigen-driven clonal expansion in the brain and CSF. Expand
Antigen-specific tolerization approaches in multiple sclerosis
TLDR
An overview of the recent and ongoing strategies to inhibit specific immune responses in MS, including different applications of myelin peptide-based approaches, T-cell vaccination, DNA vaccination and antigen-coupled cells is provided. Expand
Multiple sclerosis: a complicated picture of autoimmunity
TLDR
Recent findings obtained with both animal models and patients with multiple sclerosis indicate involvement of a T helper cell with a TH-17 phenotype, in contrast to previous data indicating that T helper type 1 cells are critical. Expand
Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines
  • R. Hohlfeld, H. Wekerle
  • Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2004
TLDR
Advances in MS therapy will depend on the growing understanding of the pathogenesis of this still incurable disease, and several innovative immunotherapies have been successfully applied in experimental autoimmune encephalomyelitis. Expand
High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model1
TLDR
This model, encompassing pathologically relevant, spontaneous disease with the presentation of myelin epitopes in the context of HLA-DR15, should offer new insights and predictions about T cell responses during MS as well as a more stringent test bed for immunotherapies. Expand
Antigen-Specific Tolerance by Autologous Myelin Peptide–Coupled Cells: A Phase 1 Trial in Multiple Sclerosis
TLDR
This first-in-man clinical trial of autologous peptide-coupled cells in MS patients establishes the feasibility and indicates good tolerability and safety of this therapeutic approach. Expand
Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research.
TLDR
Critically discuss models of experimental autoimmune encephalomyelitis that reproduce specific features of the histopathology and neurobiology of multiple sclerosis and their shortcomings as tools to investigate emerging therapeutic approaches. Expand
The re-emergence of antigen-specific tolerance as a potential therapy for MS
Ideal therapy for inflammatory disease in the nervous system would preserve normal immune function, while suppressing only the pathologic immune responses that damage tissue and allowing for repair.Expand
Immunology of multiple sclerosis.
TLDR
It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future. Expand
T cell vaccination in multiple sclerosis: a preliminary report.
TLDR
It is concluded that the use of attenuated autoreactive T cell clones appears feasible for further clinical trials in humans with autoimmune diseases. Expand
...
1
2
3
4
5
...