Immune engineered extracellular vesicles to modulate T cell activation in the context of type 1 diabetes

Sci Adv. 2023 Jun 2;9(22):eadg1082. doi: 10.1126/sciadv.adg1082. Epub 2023 Jun 2.

Abstract

Extracellular vesicles (EVs) can affect immune responses through antigen presentation and costimulation or coinhibition. We generated designer EVs to modulate T cells in the context of type 1 diabetes, a T cell-mediated autoimmune disease, by engineering a lymphoblast cell line, K562, to express HLA-A*02 (HLA-A2) alongside costimulatory CD80 and/or coinhibitory programmed death ligand 1 (PD-L1). EVs presenting HLA-A2 and CD80 activated CD8+ T cells in a dose, antigen, and HLA-specific manner. Adding PD-L1 to these EVs produced an immunoregulatory response, reducing CD8+ T cell activation and cytotoxicity in vitro. EVs alone could not stimulate T cells without antigen-presenting cells. EVs lacking CD80 were ineffective at modulating CD8+ T cell activation, suggesting that both peptide-HLA complex and costimulation are required for EV-mediated immune modulation. These results provide mechanistic insight into the rational design of EVs as a cell-free approach to immunotherapy that can be tailored to promote inflammatory or tolerogenic immune responses.

MeSH terms

  • B7-H1 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Diabetes Mellitus, Type 1* / metabolism
  • Diabetes Mellitus, Type 1* / therapy
  • Extracellular Vesicles* / metabolism
  • HLA-A2 Antigen / metabolism
  • Humans

Substances

  • B7-H1 Antigen
  • HLA-A2 Antigen