Impact Factor 6.429

The 5th most cited journal in Immunology

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.00281

Tolerogenic Nanoparticles Induce Antigen-Specific Regulatory T Cells and Provide Therapeutic Efficacy and Transferrable Tolerance Against Experimental Autoimmune Encephalomyelitis

 Robert A. LaMothe1, Pallavi Kolte1,  Trinh Vo1,  Tracy C. Gelsinger1,  Jodie Wong2, Victor T. Chan1, Sinthia Ahmed1, Aditi Srinivasan1, Patrick Deitemeyer1,  Roberto A. Maldonado1 and  Takashi K. Kishimoto1*
  • 1Selecta Biosciences (United States), United States
  • 2Northeastern University, United States

T cells reacting to self-components can promote tissue damage when escaping tolerogenic control mechanisms and may result in autoimmune disease. The current treatments for these disorders are not antigen-specific and can compromise host immunity. We have previously demonstrated that tolerogenic nanoparticles (tNPs) comprised of biodegradable polymers that encapsulate rapamycin co-administered with encapsulated or free antigen (Ag) are capable of inhibiting antigen-specific transgenic T cell proliferation and inducing antigen-specific regulatory T cells (Tregs). Here we further show that tNPs can trigger the expansion of endogenous Tregs specific to a target antigen. The proportion of antigen-specific Treg to total antigen-specific T cells remains constant even after subsequent antigen challenge in combination with a potent TLR7/8 agonist or complete Freunds adjuvant (CFA). Treatment with tNPs provide therapeutic protection in relapsing experimental autoimmune encephalomyelitis (rEAE) that can be transferred to naïve animals. Furthermore, mice treated with tNPs do not develop EAE after adoptive transfer of encephalitogenic T cells. These findings describe a potent therapy to expand Ag-specific Tregs in-vivo and suppress T cell-mediated autoimmunity.

Keywords: Nanoparticles, immunological tolerance, rapamycin, regulatory T cells, Anti-drug antibodies

Received: 15 Sep 2017; Accepted: 31 Jan 2018.

Edited by:

John Isaacs, Newcastle University, United Kingdom

Reviewed by:

Bruce M. Hall, University of New South Wales, Australia
Alf Hamann, Deutsches Rheuma-Forschungszentrum (DRFZ), Germany
Andrew L. Mellor, Newcastle University, United Kingdom  

Copyright: © 2018 LaMothe, Kolte, Vo, Gelsinger, Wong, Chan, Ahmed, Srinivasan, Deitemeyer, Maldonado and Kishimoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Takashi K. Kishimoto, Selecta Biosciences (United States), Watertown, United States,