Analysis of therapeutic potential of monocytic myeloid-derived suppressor cells in cardiac allotransplantation.
Adoptive Transfer
Animals
Cells, Cultured
Disease Models, Animal
Graft Rejection
/ therapy
Graft Survival
Heart Transplantation
Humans
Immunosuppression Therapy
/ methods
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Monocytes
/ immunology
Myeloid-Derived Suppressor Cells
/ immunology
Nitric Oxide Synthase Type II
/ metabolism
T-Lymphocytes, Regulatory
/ immunology
Transplantation, Homologous
Heart transplantation
Myeloid-derived suppressor cells
Regulatory T cells
Journal
Transplant immunology
ISSN: 1878-5492
Titre abrégé: Transpl Immunol
Pays: Netherlands
ID NLM: 9309923
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
03
12
2020
revised:
12
04
2021
accepted:
06
05
2021
pubmed:
12
5
2021
medline:
28
12
2021
entrez:
11
5
2021
Statut:
ppublish
Résumé
Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are attractive immune cells to induce immune tolerance. To explore a strategy for improving the efficacy of MDSC therapies, we examined the impact of adoptive transfer of several types of MDSCs on graft rejection in a murine heart transplantation model. We analyzed the effects of induced syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) on graft survival and suppressive capacity. We also compared the ability of syngeneic monocytic MDSCs (Mo-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) to inhibit graft rejection and investigated the suppression mechanisms. Both syngeneic and allogeneic donor- or allogeneic third-party-derived BM-MDSCs prolonged graft survival, although syngeneic BM-MDSCs inhibited anti-donor immune responses most effectively in vitro. Syngeneic Mo-MDSCs, rather than PMN-MDSCs, were responsible for immune suppression through downregulating inducible nitric oxide synthase (iNOS) and expanded naturally occurring thymic originated Treg (nTreg) in vitro. Adoptive transfer of Mo-MDSCs, but not PMN-MDSCs, prolonged graft survival and increased Treg infiltration into the graft heart. Recipient-derived Mo-MDSCs are most effective in prolonging graft survival via inhibiting T cell response and nTreg infiltration.
Sections du résumé
BACKGROUND
Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are attractive immune cells to induce immune tolerance. To explore a strategy for improving the efficacy of MDSC therapies, we examined the impact of adoptive transfer of several types of MDSCs on graft rejection in a murine heart transplantation model.
METHODS
We analyzed the effects of induced syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) on graft survival and suppressive capacity. We also compared the ability of syngeneic monocytic MDSCs (Mo-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) to inhibit graft rejection and investigated the suppression mechanisms.
RESULTS
Both syngeneic and allogeneic donor- or allogeneic third-party-derived BM-MDSCs prolonged graft survival, although syngeneic BM-MDSCs inhibited anti-donor immune responses most effectively in vitro. Syngeneic Mo-MDSCs, rather than PMN-MDSCs, were responsible for immune suppression through downregulating inducible nitric oxide synthase (iNOS) and expanded naturally occurring thymic originated Treg (nTreg) in vitro. Adoptive transfer of Mo-MDSCs, but not PMN-MDSCs, prolonged graft survival and increased Treg infiltration into the graft heart.
CONCLUSION
Recipient-derived Mo-MDSCs are most effective in prolonging graft survival via inhibiting T cell response and nTreg infiltration.
Identifiants
pubmed: 33975012
pii: S0966-3274(21)00045-9
doi: 10.1016/j.trim.2021.101405
pii:
doi:
Substances chimiques
Nitric Oxide Synthase Type II
EC 1.14.13.39
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101405Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.