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

Amar Singh, Sabarinathan Ramachandran, Melanie L. Graham, Saeed Daneshmandi, David Heller, Wilma Lucia Suarez-Pinzon, Appakalai N. Balamurugan, Jeffrey D. Ansite, Joshua J. Wilhelm, Amy Yang, Ying Zhang, Nagendra P. Palani, Juan E. Abrahante, Christopher Burlak, Stephen D. Miller (), Xunrong Luo () and Bernhard J. Hering ()
Additional contact information
Amar Singh: University of Minnesota
Sabarinathan Ramachandran: University of Minnesota
Melanie L. Graham: University of Minnesota
Saeed Daneshmandi: Northwestern University Feinberg School of Medicine
David Heller: University of Minnesota
Wilma Lucia Suarez-Pinzon: University of Minnesota
Appakalai N. Balamurugan: University of Minnesota
Jeffrey D. Ansite: University of Minnesota
Joshua J. Wilhelm: University of Minnesota
Amy Yang: Northwestern University Feinberg School of Medicine
Ying Zhang: University of Minnesota
Nagendra P. Palani: University of Minnesota Genomics Center
Juan E. Abrahante: University of Minnesota Informatics Institute
Christopher Burlak: University of Minnesota
Stephen D. Miller: Northwestern University
Xunrong Luo: Northwestern University Feinberg School of Medicine
Bernhard J. Hering: University of Minnesota

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract 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.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-11338-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11338-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-11338-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().