Santamaria, PedroAmbalavanan, Poornima2015-10-072015-10-072015Ambalavanan, P. (2015). Expanding Antigen-specific Tr1 Cells to Treat Autoimmunity (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26040http://hdl.handle.net/11023/2613The goal of a therapy against autoimmune diseases would be to blunt immune responses against self antigens, without impairing systemic immunity. Our lab has been developing a nanoparticle-based therapy which consists of disease-relevant peptide-MHC complexes coated on iron-oxide nanoparticles (NPs). We have demonstrated that the therapeutic effects exerted by these NPs are associated with expansion of antigen-specific T-regulatory-type-1 (Tr1) cells and immuno-suppression of autoantigen-loaded antigen presenting cells (APCs) in an IL-10 and TGF-beta-dependent manner. We have established that suppression is disease- and organ-specific and effective in different autoimmune diseases (EAE and CIA) and genetic background (C57BL/6 and C57BL/10). We have found that NPs coated with epitopes released downstream from a disease-triggering insult can be as effective in suppressing disease as those coated with disease-inducing epitopes. EAE-relevant pMHC II-NPs were not only effective in suppressing inflammation but also in promoting re-myelination. Thus this therapy provides a negative feedback loop that serves to counter autoimmune disease progression.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.ImmunologyAutoimmune diseaseEAETr1 cellsmaster thesis10.11575/PRISM/26040