Nathali Kaushansky
Scientific Tracks Abstracts: J Neurol Neurophysiol
It is now widely accepted that the pathogenic autoimmunity in MS, as well as in other organ-specific autoimmune diseases,
can bedirected against several target antigens. We recently showed that a concomitant ‘‘multi-epitope-targeting’’ approach,
using a specifically designed artificial multi-epitope protein (Y-MSPc) is required foreffective antigen-based immune-specific
therapy of organ-specificautoimmune diseases associated with complex and dynamic pathogenic autoimmunity, such as
MSY-MSPc was superior to peptide(s) in concomitantly downregulating pathogenic T-cells reactivity against multiple myelin
antigens/epitopes, via the induction of effective and longer lasting peripheral regulatory mechanisms (cytokine shift, anergy,
and Foxp3+ CTLA4+ regulatory T-cells . Moreover, we identified a tolerogenic myeloid DC subset in the CNS and spleen
of EAE mice playing an important role in immunoregulation process in EAE, following Y-MSPc treatment. Our results
demonstrate that immune tolerance induced by Y-MSPc is associated by increase of CD11c+CD11b+Gr1 myeloid derived
dendritic cells in the CNS and spleen. These myeloid DCs exhibited immunoregulatory characteristics, including increased
production of IL-4, IL-10 and TGF-b but reduced IL-12. Furthermore, CD11c+CD11b+Gr1 DCs were also capable of inhibiting
the proliferation of PLP139-151-specific T cells in vitro and significantly suppressed ongoing EAE upon adaptive transfer. In
addition, adaptive transfer of CD11c+CD11b+Gr1 DCs derived from YMSPc treated mice to EAE induced mice resulted in
remarkably upregulation of CD4FOXP3 regulatory cells. Taken together, these findings suggest that i.v. administration of
the multi epitope protein (Y-MSPc) results in maintaining peripheral tolerance and reduce EAE incidence by an increase in
tolerogenic CD11c+CD11b+Gr1.
Nathali Kaushansky, PhD, is a staff scientist in the Neurobiology Department at the Weizmann institute of Science. She has received her BSc in Chemistry and MSc
in Biomedical Engineering from the Technion – Israel Institute of Technology, Israel. She completed her PhD studies and post-doctoral training in the Immunology
Department in The Weizmann Institute of Science.
In the last 10 years she work has focused on characterization of autoimmune T- and B-cells against myelin and neuronal target antigensin Multiple Sclerosis
(MS). Her study aims to establish a highly specific “multi – targeting” immunemodulatory approach via co-antagonizing of most known and potentially pathogenic
T-cell autoreactivities in MS. The primary goals of her recent research were1: studying mechanisms underlying immunomodulation by this multi epitope targeting
agent (specificallydesigned artificial multi-epitope protein (Y-MSPc)-recently published) and 2: studying immunogenetics of susceptibility to MS, mainly at defining
HLA-DR2-related epitopes of the different most important myelin target antigens in MS.
