Adoptive transfer of regulatory T (Treg) cells have been employed effectively for suppression of several animal models for autoimmune diseases. In order to employ Treg cell therapy in patients, it is necessary to generate Treg cells from the patient's own cells (autologous) that would be able to suppress effectively the disease in vivo, upon their reintroduction to the patient. Towards this objective, we report in the present study on a protocol for a successful immune-regulation of experimental autoimmune myasthenia gravis (EAMG) by ex vivo - generated autologous Treg cells. For this protocol bone marrow (BM) cells, are first cultured in the presence of GM-CSF, giving rise to a population of CD11c+MHCII+CD45RA+CD8- DCs (BMDCs). Splenic CD4+ T cells are then co-cultured with the differentiated BM cells and expand to 90% of Foxp3+ Treg cells. In vitro assay exhibits a similar dose dependent manner in the suppression of T effector cells proliferation between Treg cells obtained from either healthy or sick donors. In addition, both Treg cells inhibit similarly the secretion of IFN-γ from activated splenocytes. Administration of 1 × 106 ex-vivo generated Treg cells, I.V, to EAMG rats, modulates the disease following a single treatment, given 3 days or 3 weeks after disease induction. Similar disease inhibition was achieved when CD4 cells were taken from either healthy or sick donors. The disease suppression was accompanied by reduced levels of total AChR specific antibodies in the serum. Moreover, due to the polyclonality of the described Treg cell, we have examined whether this treatment approach could be also employed for the treatment of other autoimmune diseases involving Treg cells. Indeed, we demonstrated that the ex-vivo generated autologous Treg cells suppress Adjuvant Arthritis (AA) in rats.This study opens the way for the application of induced autologous Treg cell therapy for myasthenia gravis, as well as for other human autoimmune diseases involving Treg cells.
|Number of pages||8|
|Journal||Journal of Autoimmunity|
|State||Published - 1 Feb 2016|
Bibliographical noteFunding Information:
Supported by grants from The Muscular Dystrophy Association of America (MDA) , The Association Francaise Contre les Myopathies (AFM) , The European Commission (FIGHT-MG, contract # FP7 HEALTH-2009-242-210.), Eurothymaide , of the EU (contract # LSHB-CT-2003-503410) and The Chief Scientist Office , Israel Ministry of Health . We thank Dr. Sonia Berrih-Aknin for her continuous help and encouragement throughout this research, and Raanan Margalit (Science in Action, Rehovot, Israel) for his help with the Adjuvant Arthritis rat model.
© 2015 Elsevier Ltd.
Copyright 2017 Elsevier B.V., All rights reserved.
- Adjuvant arthritis
- Dendritic cells
- Myasthenia gravis
- T regulatory cells