11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Suppression of experimental autoimmune myasthenia gravis by autologous T regulatory cells.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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 × 10(6) 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.

          Related collections

          Author and article information

          Journal
          J. Autoimmun.
          Journal of autoimmunity
          1095-9157
          0896-8411
          Feb 2016
          : 67
          Affiliations
          [1 ] Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
          [2 ] Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: sara.fuchs@weizmann.ac.il.
          [3 ] Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel; Department of Natural Sciences, The Open University of Israel, Raanana 43107, Israel.
          Article
          S0896-8411(15)30044-5
          10.1016/j.jaut.2015.09.005
          26489998
          Copyright © 2015 Elsevier Ltd. All rights reserved.

          Comments

          Comment on this article