Regulatory T Cells Induced by Single-Peptide Liposome Immunotherapy Suppress Islet-Specific T Cell Responses to Multiple Antigens and Protect from Autoimmune Diabetes
| Autor: | Emma E. Hamilton-Williams, Ranjeny Thomas, Anne-Sophie Bergot, Meghna Talekar, Casey M. Wright, Sumana Cikaluru, Jennifer Loaiza Naranjo, Guoliang Zheng, Irina Buckle |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer medicine.medical_treatment T cell Immunology Autoimmunity Mice SCID CD8-Positive T-Lymphocytes medicine.disease_cause Autoantigens T-Lymphocytes Regulatory Article Autoimmune Diseases Islets of Langerhans Mice Immune system Antigen Mice Inbred NOD medicine Immune Tolerance Immunology and Allergy Animals NOD mice Chemistry FOXP3 Immunotherapy medicine.anatomical_structure Diabetes Mellitus Type 1 Liposomes Cancer research Female Peptides |
| Zdroj: | J Immunol |
| ISSN: | 1550-6606 |
| Popis: | Ag-specific tolerizing immunotherapy is considered the optimal strategy to control type 1 diabetes, a childhood disease involving autoimmunity toward multiple islet antigenic peptides. To understand whether tolerizing immunotherapy with a single peptide could control diabetes driven by multiple Ags, we coencapsulated the high-affinity CD4+ mimotope (BDC2.5mim) of islet autoantigen chromogranin A (ChgA) with or without calcitriol (1α,25-dihydroxyvitamin D3) into liposomes. After liposome administration, we followed the endogenous ChgA-specific immune response with specific tetramers. Liposome administration s.c., but not i.v., induced ChgA-specific Foxp3+ and Foxp3− PD1+ CD73+ ICOS+ IL-10+ peripheral regulatory T cells in prediabetic mice, and liposome administration at the onset of hyperglycemia significantly delayed diabetes progression. After BDC2.5mim/calcitriol liposome administration, adoptive transfer of CD4+ T cells suppressed the development of diabetes in NOD severe combined immunodeficiency mice receiving diabetogenic splenocytes. After BDC2.5mim/calcitriol liposome treatment and expansion of ChgA-specific peripheral regulatory T cells. IFN-γ production and expansion of islet-specific glucose-6-phosphatase catalytic subunit–related protein–specific CD8+ T cells were also suppressed in pancreatic draining lymph node, demonstrating bystander tolerance at the site of Ag presentation. Thus, liposomes encapsulating the single CD4+ peptide, BDC2.5mim, and calcitriol induce ChgA-specific CD4+ T cells that regulate CD4+ and CD8+ self-antigen specificities and autoimmune diabetes in NOD mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|