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Long-term tolerance of islet allografts in nonhuman primates induced by apoptotic donor leukocytes.

Nature communications | 2019

Immune tolerance to allografts has been pursued for decades as an important goal in transplantation. Administration of apoptotic donor splenocytes effectively induces antigen-specific tolerance to allografts in murine studies. Here we show that two peritransplant infusions of apoptotic donor leukocytes under short-term immunotherapy with antagonistic anti-CD40 antibody 2C10R4, rapamycin, soluble tumor necrosis factor receptor and anti-interleukin 6 receptor antibody induce long-term (≥1 year) tolerance to islet allografts in 5 of 5 nonsensitized, MHC class I-disparate, and one MHC class II DRB allele-matched rhesus macaques. Tolerance in our preclinical model is associated with a regulatory network, involving antigen-specific Tr1 cells exhibiting a distinct transcriptome and indirect specificity for matched MHC class II and mismatched class I peptides. Apoptotic donor leukocyte infusions warrant continued investigation as a cellular, nonchimeric and translatable method for inducing antigen-specific tolerance in transplantation.

Pubmed ID: 31375697 RIS Download

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: DP2 DK083099
  • Agency: NIH HHS, United States
    Id: R24 OD010976
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI114824
  • Agency: NIAID NIH HHS, United States
    Id: U24 AI126683
  • Agency: NIAID NIH HHS, United States
    Id: U01 AI102463

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