Synthetically glycosylated antigens induce antigen-specific tolerance and prevent the onset of diabetes
| Autor: | Jeffrey A. Hubbell, D. Scott Wilson, Brunggel Kym, Xavier Quaglia-Thermes, Sachiko Hirosue, Giacomo Diaceri, Martina Damo, Michal M. Raczy |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Adoptive cell transfer Acetylgalactosamine T-Lymphocytes Antigen presentation Biomedical Engineering Medicine (miscellaneous) Bioengineering Spleen Mice SCID CD8-Positive T-Lymphocytes Autoantigens Immune tolerance Acetylglucosamine 03 medical and health sciences Mice 0302 clinical medicine Immune system Antigen Mice Inbred NOD Diabetes mellitus medicine Immune Tolerance Animals Antigen Presentation business.industry medicine.disease Adoptive Transfer Computer Science Applications Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Diabetes Mellitus Type 1 Liver Immunology Female business 030217 neurology & neurosurgery CD8 Biotechnology |
| Zdroj: | Nature biomedical engineering. 3(10) |
| ISSN: | 2157-846X |
| Popis: | Homeostatic antigen presentation by hepatic antigen-presenting cells, which results in tolerogenic T-cell education, could be exploited to induce antigen-specific immunological tolerance. Here we show that antigens modified with polymeric forms of either N-acetylgalactosamine or N-acetylglucosamine target hepatic antigen-presenting cells, increase their antigen presentation and induce antigen-specific tolerance, as indicated by CD4+ and CD8+ T-cell deletion and anergy. These synthetically glycosylated antigens also expanded functional regulatory T cells, which are necessary for the durable suppression of antigen-specific immune responses. In an adoptive-transfer mouse model of type-1 diabetes, treatment with the glycosylated autoantigens prevented T-cell-mediated diabetes, expanded antigen-specific regulatory T cells and resulted in lasting tolerance to a subsequent challenge with activated diabetogenic T cells. Glycosylated autoantigens targeted to hepatic antigen-presenting cells might enable therapies that promote immune tolerance in patients with autoimmune diseases. Glycosylated peptides targeting hepatic antigen-presenting cells induce antigen-specific immune tolerance, preventing T-cell-mediated diabetes in mice. |
| Databáze: | OpenAIRE |
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