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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Singh, A; Ramachandran, S; Graham, ML; Daneshmandi, S; Heller, D; Suarez-Pinzon, WL; Balamurugan, AN; Ansite, JD; Wilhelm, JJ; Yang, A; Zhang, Y; Palani, NP; Abrahante, JE; Burlak, C; Miller, SD; Luo, X; Hering, BJ

Published Date

  • August 2, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 3495 -

PubMed ID

  • 31375697

Pubmed Central ID

  • 31375697

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-11338-y

Language

  • eng

Conference Location

  • England