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

T cells reacting to self-components can promote tissue damage when escaping tolerogenic control mechanisms which may result in autoimmune disease. The current treatments for these disorders are not antigen (Ag) specific and can compromise host immunity through chronic suppression. We have previously...

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Bibliographic Details
Published in:Frontiers in immunology 2018-03, Vol.9, p.281-281
Main Authors: LaMothe, Robert A, Kolte, Pallavi N, Vo, Trinh, Ferrari, Joseph D, Gelsinger, Tracy C, Wong, Jodie, Chan, Victor T, Ahmed, Sinthia, Srinivasan, Aditi, Deitemeyer, Patrick, Maldonado, Roberto A, Kishimoto, Takashi K
Format: Article
Language:English
Subjects:
Animals
Autoantigens - immunology
Encephalomyelitis, Autoimmune, Experimental - immunology
experimental autoimmune encephalomyelitis
Female
Immune Tolerance - immunology
immunological tolerance
Immunology
Immunosuppressive Agents - administration & dosage
Mice
Nanoparticles
rapamycin
regulatory T cells
Sirolimus - administration & dosage
T-Lymphocytes, Regulatory - immunology
Vaccines, Synthetic - immunology
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Summary:T cells reacting to self-components can promote tissue damage when escaping tolerogenic control mechanisms which may result in autoimmune disease. The current treatments for these disorders are not antigen (Ag) specific and can compromise host immunity through chronic suppression. We have previously demonstrated that co-administration of encapsulated or free Ag with tolerogenic nanoparticles (tNPs) comprised of biodegradable polymers that encapsulate rapamycin are capable of inhibiting Ag-specific transgenic T cell proliferation and inducing Ag-specific regulatory T cells (Tregs). Here, we further show that tNPs can trigger the expansion of endogenous Tregs specific to a target Ag. The proportion of Ag-specific Treg to total Ag-specific T cells remains constant even after subsequent Ag challenge in combination with a potent TLR7/8 agonist or complete Freund's adjuvant. tNP-treated mice do not develop experimental autoimmune encephalomyelitis (EAE) after adoptive transfer of encephalitogenic T cells; furthermore, tNP treatment provided therapeutic protection in relapsing EAE that was transferred to naïve animals. These findings describe a potent therapy to expand Ag-specific Tregs and suppress T cell-mediated autoimmunity.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.00281