Page 4 - ISNI abstracts

International Joint Israel-Greek-Italian Neuroimmunological meeting Autologous Regulatory (Treg) Cells Generated Ex-vivo, Suppress Autoimmune Diseases Revital Aricha , Debby Reuveni , Miriam Souroujon , Sara Fuchs 1 2 1 1 1 Immunology, Weizmann Institute of Science, Israel 2 Natural Science, Open University, Israel Adoptive transfer of regulatory T (Treg) cells effectively suppresses disease in murine models of autoimmunity. In our previous studies in experimental autoimmune myasthenia gravis (EAMG) we have shown that ex-vivo generated Treg cells transferred from healthy rat donors to myasthenic rats suppressed EAMG. However, such ex-vivo generated Treg cells from sick animals did not have the same in vivo suppressive capacities as those from healthy donors. In order to proceed toward autologous cellular treatment of patients, the objective of the present study was to generate Treg cells from sick objects that would be able to suppress effectively the disease in vivo. Bone marrow (BM) cells, when cultured in the presence of GM-CSF, gave rise to a population of CD11c+MHCII+CD45RA+CD8–DCs (BMDCs), which were able to expand 70-90% of Foxp3+ Treg cells upon co-culture with CD4+ T cells. In vitro assay showed 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 inhibited similarly the secretion of IFN-g from activated splenocytes. Administration of 1x106 ex-vivo generated Treg cells, I.V, to EAMG rats, modulates the disease following a single treatment given 2 days or 3 weeks after disease induction. Similar disease inhibition was achieved when Treg cells were taken from either healthy or sick donors. The disease suppression was accompanied by a reduced levels of total AChR specific antibodies in the serum. This study opens the way for the application of induced autologous Treg cellular therapy for myasthenia gravis and generally for human autoimmune diseases involving Treg cells. 4