Tolerance of a Vascularized Composite Allograft Achieved in MHC Class-I-mismatch Swine

Animals Chimerism Composite Tissue Allografts / transplantation Immune Tolerance / physiology Kidney Transplantation Swine Transplantation Tolerance
MHC class I Vascularized composite allotransplantation (VCA) bone marrow transplantation co-stimulatory blockade mixed chimerism skin tolerance

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 05 12 2021
accepted: 15 04 2022
entrez: 27 5 2022
pubmed: 28 5 2022
medline: 31 5 2022
Statut: epublish

Résumé

Vascularized composite allografts (VCAs) allow reconstruction of devastating injuries and amputations, yet require lifelong immunosuppression that is associated with significant morbidity. Induction of immune tolerance of VCAs would permit widespread use of these procedures. VCAs are acquired from deceased donors most likely to be Swine were treated with non-myeloablative total body and thymic irradiation two days prior to infusion of bone marrow cells from an MHC class I-mismatched donor. They also received a short-term treatment with CTLA4-Ig (Belatacept Stable mixed chimerism and tolerance of MHC class-I-mismatched VCAs was achieved in 3 recipients. Allograft tolerance was associated with a sustained lack of anti-donor T cell response and a concomitant expansion of double negative CD4 This study demonstrates the first successful mixed chimerism-induced VCA tolerance in a large animal model across a MHC class-I-mismatch. Future studies aimed at fully-mismatched donor-recipient pairs are under investigation with this protocol.

Sections du résumé

Background
Vascularized composite allografts (VCAs) allow reconstruction of devastating injuries and amputations, yet require lifelong immunosuppression that is associated with significant morbidity. Induction of immune tolerance of VCAs would permit widespread use of these procedures. VCAs are acquired from deceased donors most likely to be
Methods
Swine were treated with non-myeloablative total body and thymic irradiation two days prior to infusion of bone marrow cells from an MHC class I-mismatched donor. They also received a short-term treatment with CTLA4-Ig (Belatacept
Results
Stable mixed chimerism and tolerance of MHC class-I-mismatched VCAs was achieved in 3 recipients. Allograft tolerance was associated with a sustained lack of anti-donor T cell response and a concomitant expansion of double negative CD4
Conclusions
This study demonstrates the first successful mixed chimerism-induced VCA tolerance in a large animal model across a MHC class-I-mismatch. Future studies aimed at fully-mismatched donor-recipient pairs are under investigation with this protocol.

Identifiants

DOI: 10.3389/fimmu.2022.829406 PMID: 35619720 PMC: PMC9128064
pubmed: 35619720
doi: 10.3389/fimmu.2022.829406
pmc: PMC9128064
doi:

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

829406

Informations de copyright

Copyright © 2022 Lellouch, Andrews, Saviane, Ng, Schol, Goutard, Gama, Rosales, Colvin, Lantieri, Randolph, Benichou and Cetrulo.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Nat Commun. 2015 Jul 07;6:7566
pubmed: 26151823
Am J Transplant. 2014 Feb;14(2):343-55
pubmed: 24405666
Lancet. 1999 Apr 17;353(9161):1315-20
pubmed: 10218530
Bone Marrow Transplant. 2012 Oct;47(10):1332-7
pubmed: 22307018
Lancet. 2017 Sep 9;390(10099):1038-1047
pubmed: 28823494
Transplantation. 2000 Jul 27;70(2):272-9
pubmed: 10933148
Transplantation. 2004 Feb 27;77(4):514-21
pubmed: 15084927
Curr Opin Organ Transplant. 2015 Aug;20(4):406-11
pubmed: 26147679
Lancet. 2015 Jun 13;385(9985):2352-3
pubmed: 26088638
J Immunogenet. 1984 Feb;11(1):9-19
pubmed: 6231343
Tissue Antigens. 1999 Jul;54(1):43-52
pubmed: 10458322
Am J Transplant. 2010 Jul;10(7):1524-33
pubmed: 20642679
Nat Med. 2014 Jul;20(7):790-3
pubmed: 24973919
Curr Transplant Rep. 2014 Sep 1;1(3):137-146
pubmed: 25435071
J Surg Res. 2021 Feb;258:17-22
pubmed: 32977237
Transpl Int. 2019 Jul;32(7):693-701
pubmed: 30633815
Transplantation. 1976 Dec;22(6):559-67
pubmed: 137560
Am J Transplant. 2014 Jul;14(7):1599-611
pubmed: 24903438
Am J Transplant. 2017 Jul;17(7):1729-1741
pubmed: 28035752
N Engl J Med. 2013 May 9;368(19):1850-2
pubmed: 23656665
Am J Transplant. 2008 Jul;8(7):1396-400
pubmed: 18444912
Lancet. 2020 Nov 28;396(10264):1758-1765
pubmed: 33248497
Am J Transplant. 2011 May;11(5):936-46
pubmed: 21449942

Auteurs

Alexandre G Lellouch (AG)

Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Service de Chirurgie Plastique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (APHP), Université Paris Descartes, Paris, France.
Shriners Hospitals for Children, Harvard Medical School, Boston, MA, United States.

Alec R Andrews (AR)

Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Shriners Hospitals for Children, Harvard Medical School, Boston, MA, United States.

Gaelle Saviane (G)

Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Shriners Hospitals for Children, Harvard Medical School, Boston, MA, United States.
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Zhi Yang Ng (ZY)

Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Ilse M Schol (IM)

Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Marion Goutard (M)

Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Service de Chirurgie Plastique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (APHP), Université Paris Descartes, Paris, France.
Shriners Hospitals for Children, Harvard Medical School, Boston, MA, United States.

Amon-Ra Gama (AR)

Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Ivy A Rosales (IA)

Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Robert B Colvin (RB)

Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Laurent A Lantieri (LA)

Service de Chirurgie Plastique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (APHP), Université Paris Descartes, Paris, France.

Mark A Randolph (MA)

Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Shriners Hospitals for Children, Harvard Medical School, Boston, MA, United States.

Gilles Benichou (G)

Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Curtis L Cetrulo (CL)

Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Shriners Hospitals for Children, Harvard Medical School, Boston, MA, United States.
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

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Classifications MeSH

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questionsmedicales.fr › Régions du corps › Transplants › Allogreffes de tissus composites › Tolerance of a Vascularized Composite...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunomodulation › Tolérance immunitaire › Tolerance of a Vascularized Composite...
questionsmedicales.fr › Procédures de chirurgie opératoire › Procédures de chirurgie urogénitale › Procédures de chirurgie urologique › Transplantation rénale › Tolerance of a Vascularized Composite...
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questionsmedicales.fr › Phénomènes du système immunitaire › Immunomodulation › Tolérance immunitaire › Tolérance à la transplantation › Tolerance of a Vascularized Composite...