Long-term tolerance of islet allografts in nonhuman primates induced by apoptotic donor leukocytes.
Adoptive Transfer
Allografts
/ immunology
Animals
Apoptosis
/ immunology
Disease Models, Animal
Female
Graft Rejection
/ immunology
Graft Survival
/ immunology
Humans
Immune Tolerance
Immunosuppressive Agents
/ therapeutic use
Islets of Langerhans
/ immunology
Islets of Langerhans Transplantation
/ adverse effects
Macaca mulatta
Male
T-Lymphocytes, Regulatory
/ immunology
Tissue Donors
Transplantation, Homologous
/ adverse effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 08 2019
02 08 2019
Historique:
received:
28
11
2018
accepted:
09
07
2019
entrez:
4
8
2019
pubmed:
4
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31375697
doi: 10.1038/s41467-019-11338-y
pii: 10.1038/s41467-019-11338-y
pmc: PMC6677762
doi:
Substances chimiques
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3495Subventions
Organisme : NIDDK NIH HHS
ID : DP2 DK083099
Pays : United States
Organisme : NIH HHS
ID : R24 OD010976
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI114824
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI126683
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI102463
Pays : United States
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