The Mechanism of Action of Antigen Processing Independent T Cell Epitopes Designed for Immunotherapy of Autoimmune Diseases
| Autor: | Brecht Hoedemaekers, Evelien Schurgers, Sarah Aerts, Heather B Streeter, Ella R. Shepard, Sky T. H. Ng, Anja Wegner, Lotta Jansson, Elaine V. Hill, Bronwen R Burton, David C. Wraith |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Encephalomyelitis Autoimmune Experimental dendritic cell T cell medicine.medical_treatment Immunology interleukin-10 Antigen-Presenting Cells Epitopes T-Lymphocyte Autoimmunity Mice Transgenic autoimmune disease apitope Biology Lymphocyte Activation Autoimmune Diseases 03 medical and health sciences Mice 0302 clinical medicine synthetic peptide medicine Immune Tolerance Immunology and Allergy Animals Antigen-presenting cell Original Research Autoimmune disease Antigen Presentation Antigen processing FOXP3 Dendritic cell Immunotherapy medicine.disease Interleukin 10 Disease Models Animal Tr1 cell 030104 developmental biology medicine.anatomical_structure Cancer research Cytokines immunotherapy Peptides lcsh:RC581-607 immunological tolerance 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | Immunotherapy with antigen-processing independent T cell epitopes (apitopes) targeting autoreactive CD4+ T cells has translated to the clinic and been shown to modulate progression of both Graves’ disease and multiple sclerosis. The model apitope (Ac1-9[4Y]) renders antigen-specific T cells anergic while repeated administration induces both Tr1 and Foxp3+ regulatory cells. Here we address why CD4+ T cell epitopes should be designed as apitopes to induce tolerance and define the antigen presenting cells that they target in vivo. Furthermore, we reveal the impact of treatment with apitopes on CD4+ T cell signaling, the generation of IL-10-secreting regulatory cells and the systemic migration of these cells. Taken together these findings reveal how apitopes induce tolerance and thereby mediate antigen-specific immunotherapy of autoimmune diseases. |
| Databáze: | OpenAIRE |
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