Long-term tolerance of islet allografts in nonhuman primates induced by apoptotic donor leukocytes.
Identifieur interne : 000292 ( Main/Exploration ); précédent : 000291; suivant : 000293Long-term tolerance of islet allografts in nonhuman primates induced by apoptotic donor leukocytes.
Auteurs : Amar Singh [États-Unis] ; Sabarinathan Ramachandran [États-Unis] ; Melanie L. Graham [États-Unis] ; Saeed Daneshmandi [États-Unis] ; David Heller [États-Unis] ; Wilma Lucia Suarez-Pinzon [États-Unis] ; Appakalai N. Balamurugan [États-Unis] ; Jeffrey D. Ansite [États-Unis] ; Joshua J. Wilhelm [États-Unis] ; Amy Yang [États-Unis] ; Ying Zhang [États-Unis] ; Nagendra P. Palani [États-Unis] ; Juan E. Abrahante [États-Unis] ; Christopher Burlak [États-Unis] ; Stephen D. Miller [États-Unis] ; Xunrong Luo [États-Unis] ; Bernhard J. Hering [États-Unis]Source :
- Nature communications [ 2041-1723 ] ; 2019.
Descripteurs français
- KwdFr :
- Allogreffes (immunologie), Animaux (MeSH), Apoptose (immunologie), Donneurs de tissus (MeSH), Femelle (MeSH), Humains (MeSH), Ilots pancréatiques (immunologie), Immunosuppresseurs (usage thérapeutique), Lymphocytes T régulateurs (immunologie), Lymphocytes T régulateurs (transplantation), Macaca mulatta (MeSH), Modèles animaux de maladie humaine (MeSH), Mâle (MeSH), Rejet du greffon (immunologie), Rejet du greffon (prévention et contrôle), Survie du greffon (immunologie), Tolérance immunitaire (MeSH), Transfert adoptif (MeSH), Transplantation d'ilots de Langerhans (effets indésirables), Transplantation homologue (effets indésirables).
- MESH :
- effets indésirables : Transplantation d'ilots de Langerhans, Transplantation homologue.
- immunologie : Allogreffes, Apoptose, Ilots pancréatiques, Lymphocytes T régulateurs, Rejet du greffon, Survie du greffon.
- prévention et contrôle : Rejet du greffon.
- usage thérapeutique : Immunosuppresseurs, Lymphocytes T régulateurs.
- Animaux, Donneurs de tissus, Femelle, Humains, Macaca mulatta, Modèles animaux de maladie humaine, Mâle, Tolérance immunitaire, Transfert adoptif.
English descriptors
- KwdEn :
- Adoptive Transfer (MeSH), Allografts (immunology), Animals (MeSH), Apoptosis (immunology), Disease Models, Animal (MeSH), Female (MeSH), Graft Rejection (immunology), Graft Rejection (prevention & control), Graft Survival (immunology), Humans (MeSH), Immune Tolerance (MeSH), Immunosuppressive Agents (therapeutic use), Islets of Langerhans (immunology), Islets of Langerhans Transplantation (adverse effects), Macaca mulatta (MeSH), Male (MeSH), T-Lymphocytes, Regulatory (immunology), T-Lymphocytes, Regulatory (transplantation), Tissue Donors (MeSH), Transplantation, Homologous (adverse effects).
- MESH :
- chemical , therapeutic use : Immunosuppressive Agents.
- adverse effects : Islets of Langerhans Transplantation, Transplantation, Homologous.
- immunology : Allografts, Apoptosis, Graft Rejection, Graft Survival, Islets of Langerhans, T-Lymphocytes, Regulatory.
- prevention & control : Graft Rejection.
- transplantation : T-Lymphocytes, Regulatory.
- Adoptive Transfer, Animals, Disease Models, Animal, Female, Humans, Immune Tolerance, Macaca mulatta, Male, Tissue Donors.
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.
DOI: 10.1038/s41467-019-11338-y
PubMed: 31375697
PubMed Central: PMC6677762
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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Palani</name><affiliation wicri:level="1"><nlm:affiliation>University of Minnesota Genomics Center, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Minnesota Genomics Center, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Abrahante, Juan E" sort="Abrahante, Juan E" uniqKey="Abrahante J" first="Juan E" last="Abrahante">Juan E. 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Miller</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology-Immunology and Interdepartmental Immunology Center, Northwestern University, Chicago, IL, 60611, USA. s-d-miller@northwestern.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology-Immunology and Interdepartmental Immunology Center, Northwestern University, Chicago, IL, 60611</wicri:regionArea><wicri:noRegion>60611</wicri:noRegion></affiliation></author><author><name sortKey="Luo, Xunrong" sort="Luo, Xunrong" uniqKey="Luo X" first="Xunrong" last="Luo">Xunrong Luo</name><affiliation wicri:level="1"><nlm:affiliation>Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. xunrong.luo@duke.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611</wicri:regionArea><wicri:noRegion>60611</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. xunrong.luo@duke.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611</wicri:regionArea><wicri:noRegion>60611</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Duke Transplant Center, Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA. xunrong.luo@duke.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Transplant Center, Department of Medicine, Duke University School of Medicine, Durham, NC, 27710</wicri:regionArea><wicri:noRegion>27710</wicri:noRegion></affiliation></author><author><name sortKey="Hering, Bernhard J" sort="Hering, Bernhard J" uniqKey="Hering B" first="Bernhard J" last="Hering">Bernhard J. Hering</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA. bhering@umn.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31375697</idno><idno type="pmid">31375697</idno><idno type="doi">10.1038/s41467-019-11338-y</idno><idno type="pmc">PMC6677762</idno><idno type="wicri:Area/Main/Corpus">000221</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000221</idno><idno type="wicri:Area/Main/Curation">000221</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000221</idno><idno type="wicri:Area/Main/Exploration">000221</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Long-term tolerance of islet allografts in nonhuman primates induced by apoptotic donor leukocytes.</title><author><name sortKey="Singh, Amar" sort="Singh, Amar" uniqKey="Singh A" first="Amar" last="Singh">Amar Singh</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Ramachandran, Sabarinathan" sort="Ramachandran, Sabarinathan" uniqKey="Ramachandran S" first="Sabarinathan" last="Ramachandran">Sabarinathan Ramachandran</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Graham, Melanie L" sort="Graham, Melanie L" uniqKey="Graham M" first="Melanie L" last="Graham">Melanie L. Graham</name><affiliation wicri:level="1"><nlm:affiliation>Preclinical Research Center, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Preclinical Research Center, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Daneshmandi, Saeed" sort="Daneshmandi, Saeed" uniqKey="Daneshmandi S" first="Saeed" last="Daneshmandi">Saeed Daneshmandi</name><affiliation wicri:level="1"><nlm:affiliation>Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611</wicri:regionArea><wicri:noRegion>60611</wicri:noRegion></affiliation></author><author><name sortKey="Heller, David" sort="Heller, David" uniqKey="Heller D" first="David" last="Heller">David Heller</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Suarez Pinzon, Wilma Lucia" sort="Suarez Pinzon, Wilma Lucia" uniqKey="Suarez Pinzon W" first="Wilma Lucia" last="Suarez-Pinzon">Wilma Lucia Suarez-Pinzon</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Balamurugan, Appakalai N" sort="Balamurugan, Appakalai N" uniqKey="Balamurugan A" first="Appakalai N" last="Balamurugan">Appakalai N. Balamurugan</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Center for Cellular Transplantation, Cardiovascular Innovation Institute, Department of Surgery, University of Louisville, Louisville, KY, 40202, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Cellular Transplantation, Cardiovascular Innovation Institute, Department of Surgery, University of Louisville, Louisville, KY, 40202</wicri:regionArea><wicri:noRegion>40202</wicri:noRegion></affiliation></author><author><name sortKey="Ansite, Jeffrey D" sort="Ansite, Jeffrey D" uniqKey="Ansite J" first="Jeffrey D" last="Ansite">Jeffrey D. Ansite</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Wilhelm, Joshua J" sort="Wilhelm, Joshua J" uniqKey="Wilhelm J" first="Joshua J" last="Wilhelm">Joshua J. Wilhelm</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Amy" sort="Yang, Amy" uniqKey="Yang A" first="Amy" last="Yang">Amy Yang</name><affiliation wicri:level="1"><nlm:affiliation>Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611</wicri:regionArea><wicri:noRegion>60611</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Ying" sort="Zhang, Ying" uniqKey="Zhang Y" first="Ying" last="Zhang">Ying Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Palani, Nagendra P" sort="Palani, Nagendra P" uniqKey="Palani N" first="Nagendra P" last="Palani">Nagendra P. Palani</name><affiliation wicri:level="1"><nlm:affiliation>University of Minnesota Genomics Center, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Minnesota Genomics Center, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Abrahante, Juan E" sort="Abrahante, Juan E" uniqKey="Abrahante J" first="Juan E" last="Abrahante">Juan E. Abrahante</name><affiliation wicri:level="1"><nlm:affiliation>University of Minnesota Informatics Institute, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Minnesota Informatics Institute, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Burlak, Christopher" sort="Burlak, Christopher" uniqKey="Burlak C" first="Christopher" last="Burlak">Christopher Burlak</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author><author><name sortKey="Miller, Stephen D" sort="Miller, Stephen D" uniqKey="Miller S" first="Stephen D" last="Miller">Stephen D. Miller</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology-Immunology and Interdepartmental Immunology Center, Northwestern University, Chicago, IL, 60611, USA. s-d-miller@northwestern.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology-Immunology and Interdepartmental Immunology Center, Northwestern University, Chicago, IL, 60611</wicri:regionArea><wicri:noRegion>60611</wicri:noRegion></affiliation></author><author><name sortKey="Luo, Xunrong" sort="Luo, Xunrong" uniqKey="Luo X" first="Xunrong" last="Luo">Xunrong Luo</name><affiliation wicri:level="1"><nlm:affiliation>Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. xunrong.luo@duke.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611</wicri:regionArea><wicri:noRegion>60611</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. xunrong.luo@duke.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611</wicri:regionArea><wicri:noRegion>60611</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Duke Transplant Center, Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA. xunrong.luo@duke.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Transplant Center, Department of Medicine, Duke University School of Medicine, Durham, NC, 27710</wicri:regionArea><wicri:noRegion>27710</wicri:noRegion></affiliation></author><author><name sortKey="Hering, Bernhard J" sort="Hering, Bernhard J" uniqKey="Hering B" first="Bernhard J" last="Hering">Bernhard J. Hering</name><affiliation wicri:level="1"><nlm:affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA. bhering@umn.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455</wicri:regionArea><wicri:noRegion>55455</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nature communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adoptive Transfer (MeSH)</term><term>Allografts (immunology)</term><term>Animals (MeSH)</term><term>Apoptosis (immunology)</term><term>Disease Models, Animal (MeSH)</term><term>Female (MeSH)</term><term>Graft Rejection (immunology)</term><term>Graft Rejection (prevention & control)</term><term>Graft Survival (immunology)</term><term>Humans (MeSH)</term><term>Immune Tolerance (MeSH)</term><term>Immunosuppressive Agents (therapeutic use)</term><term>Islets of Langerhans (immunology)</term><term>Islets of Langerhans Transplantation (adverse effects)</term><term>Macaca mulatta (MeSH)</term><term>Male (MeSH)</term><term>T-Lymphocytes, Regulatory (immunology)</term><term>T-Lymphocytes, Regulatory (transplantation)</term><term>Tissue Donors (MeSH)</term><term>Transplantation, Homologous (adverse effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Allogreffes (immunologie)</term><term>Animaux (MeSH)</term><term>Apoptose (immunologie)</term><term>Donneurs de tissus (MeSH)</term><term>Femelle (MeSH)</term><term>Humains (MeSH)</term><term>Ilots pancréatiques (immunologie)</term><term>Immunosuppresseurs (usage thérapeutique)</term><term>Lymphocytes T régulateurs (immunologie)</term><term>Lymphocytes T régulateurs (transplantation)</term><term>Macaca mulatta (MeSH)</term><term>Modèles animaux de maladie humaine (MeSH)</term><term>Mâle (MeSH)</term><term>Rejet du greffon (immunologie)</term><term>Rejet du greffon (prévention et contrôle)</term><term>Survie du greffon (immunologie)</term><term>Tolérance immunitaire (MeSH)</term><term>Transfert adoptif (MeSH)</term><term>Transplantation d'ilots de Langerhans (effets indésirables)</term><term>Transplantation homologue (effets indésirables)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Immunosuppressive Agents</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Islets of Langerhans Transplantation</term><term>Transplantation, Homologous</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Transplantation d'ilots de Langerhans</term><term>Transplantation homologue</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Allogreffes</term><term>Apoptose</term><term>Ilots pancréatiques</term><term>Lymphocytes T régulateurs</term><term>Rejet du greffon</term><term>Survie du greffon</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Allografts</term><term>Apoptosis</term><term>Graft Rejection</term><term>Graft Survival</term><term>Islets of Langerhans</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Graft Rejection</term></keywords><keywords scheme="MESH" qualifier="prévention et contrôle" xml:lang="fr"><term>Rejet du greffon</term></keywords><keywords scheme="MESH" qualifier="transplantation" xml:lang="en"><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Immunosuppresseurs</term><term>Lymphocytes T régulateurs</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adoptive Transfer</term><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Immune Tolerance</term><term>Macaca mulatta</term><term>Male</term><term>Tissue Donors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Donneurs de tissus</term><term>Femelle</term><term>Humains</term><term>Macaca mulatta</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Tolérance immunitaire</term><term>Transfert adoptif</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31375697</PMID><DateCompleted><Year>2019</Year><Month>12</Month><Day>16</Day></DateCompleted><DateRevised><Year>2020</Year><Month>08</Month><Day>01</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>1</Issue><PubDate><Year>2019</Year><Month>08</Month><Day>02</Day></PubDate></JournalIssue><Title>Nature communications</Title><ISOAbbreviation>Nat Commun</ISOAbbreviation></Journal><ArticleTitle>Long-term tolerance of islet allografts in nonhuman primates induced by apoptotic donor leukocytes.</ArticleTitle><Pagination><MedlinePgn>3495</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41467-019-11338-y</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Singh</LastName><ForeName>Amar</ForeName><Initials>A</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-4721-1513</Identifier><AffiliationInfo><Affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ramachandran</LastName><ForeName>Sabarinathan</ForeName><Initials>S</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-2239-8083</Identifier><AffiliationInfo><Affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Graham</LastName><ForeName>Melanie L</ForeName><Initials>ML</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-2475-6975</Identifier><AffiliationInfo><Affiliation>Preclinical Research Center, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Daneshmandi</LastName><ForeName>Saeed</ForeName><Initials>S</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-7817-3006</Identifier><AffiliationInfo><Affiliation>Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heller</LastName><ForeName>David</ForeName><Initials>D</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-0461-8524</Identifier><AffiliationInfo><Affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Suarez-Pinzon</LastName><ForeName>Wilma Lucia</ForeName><Initials>WL</Initials><AffiliationInfo><Affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Balamurugan</LastName><ForeName>Appakalai N</ForeName><Initials>AN</Initials><AffiliationInfo><Affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center for Cellular Transplantation, Cardiovascular Innovation Institute, Department of Surgery, University of Louisville, Louisville, KY, 40202, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ansite</LastName><ForeName>Jeffrey D</ForeName><Initials>JD</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-6241-0468</Identifier><AffiliationInfo><Affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wilhelm</LastName><ForeName>Joshua J</ForeName><Initials>JJ</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-6187-4874</Identifier><AffiliationInfo><Affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Amy</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-3764-7329</Identifier><AffiliationInfo><Affiliation>Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Palani</LastName><ForeName>Nagendra P</ForeName><Initials>NP</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-7701-8901</Identifier><AffiliationInfo><Affiliation>University of Minnesota Genomics Center, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abrahante</LastName><ForeName>Juan E</ForeName><Initials>JE</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-9074-4307</Identifier><AffiliationInfo><Affiliation>University of Minnesota Informatics Institute, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burlak</LastName><ForeName>Christopher</ForeName><Initials>C</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-1715-1377</Identifier><AffiliationInfo><Affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Miller</LastName><ForeName>Stephen D</ForeName><Initials>SD</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-9556-0718</Identifier><AffiliationInfo><Affiliation>Department of Microbiology-Immunology and Interdepartmental Immunology Center, Northwestern University, Chicago, IL, 60611, USA. s-d-miller@northwestern.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>Xunrong</ForeName><Initials>X</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-5581-9409</Identifier><AffiliationInfo><Affiliation>Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. xunrong.luo@duke.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. xunrong.luo@duke.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Duke Transplant Center, Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA. xunrong.luo@duke.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hering</LastName><ForeName>Bernhard J</ForeName><Initials>BJ</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-5962-7284</Identifier><AffiliationInfo><Affiliation>Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA. bhering@umn.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI114824</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U24 AI126683</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R24 OD010976</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>08</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nat Commun</MedlineTA><NlmUniqueID>101528555</NlmUniqueID><ISSNLinking>2041-1723</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007166">Immunosuppressive Agents</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D019264" MajorTopicYN="N">Adoptive Transfer</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D064591" MajorTopicYN="N">Allografts</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006084" MajorTopicYN="N">Graft Rejection</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006085" MajorTopicYN="N">Graft Survival</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007108" MajorTopicYN="Y">Immune Tolerance</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007166" MajorTopicYN="N">Immunosuppressive Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007515" MajorTopicYN="N">Islets of Langerhans</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016381" MajorTopicYN="N">Islets of Langerhans Transplantation</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008253" MajorTopicYN="N">Macaca mulatta</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D050378" MajorTopicYN="N">T-Lymphocytes, Regulatory</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000637" MajorTopicYN="Y">transplantation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014019" MajorTopicYN="N">Tissue Donors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014184" MajorTopicYN="N">Transplantation, Homologous</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>11</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>07</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>8</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>8</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>12</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31375697</ArticleId><ArticleId IdType="doi">10.1038/s41467-019-11338-y</ArticleId><ArticleId IdType="pii">10.1038/s41467-019-11338-y</ArticleId><ArticleId IdType="pmc">PMC6677762</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Singh, Amar" sort="Singh, Amar" uniqKey="Singh A" first="Amar" last="Singh">Amar Singh</name></noRegion><name sortKey="Abrahante, Juan E" sort="Abrahante, Juan E" uniqKey="Abrahante J" first="Juan E" last="Abrahante">Juan E. Abrahante</name><name sortKey="Ansite, Jeffrey D" sort="Ansite, Jeffrey D" uniqKey="Ansite J" first="Jeffrey D" last="Ansite">Jeffrey D. Ansite</name><name sortKey="Balamurugan, Appakalai N" sort="Balamurugan, Appakalai N" uniqKey="Balamurugan A" first="Appakalai N" last="Balamurugan">Appakalai N. Balamurugan</name><name sortKey="Balamurugan, Appakalai N" sort="Balamurugan, Appakalai N" uniqKey="Balamurugan A" first="Appakalai N" last="Balamurugan">Appakalai N. Balamurugan</name><name sortKey="Burlak, Christopher" sort="Burlak, Christopher" uniqKey="Burlak C" first="Christopher" last="Burlak">Christopher Burlak</name><name sortKey="Daneshmandi, Saeed" sort="Daneshmandi, Saeed" uniqKey="Daneshmandi S" first="Saeed" last="Daneshmandi">Saeed Daneshmandi</name><name sortKey="Graham, Melanie L" sort="Graham, Melanie L" uniqKey="Graham M" first="Melanie L" last="Graham">Melanie L. Graham</name><name sortKey="Heller, David" sort="Heller, David" uniqKey="Heller D" first="David" last="Heller">David Heller</name><name sortKey="Hering, Bernhard J" sort="Hering, Bernhard J" uniqKey="Hering B" first="Bernhard J" last="Hering">Bernhard J. Hering</name><name sortKey="Luo, Xunrong" sort="Luo, Xunrong" uniqKey="Luo X" first="Xunrong" last="Luo">Xunrong Luo</name><name sortKey="Luo, Xunrong" sort="Luo, Xunrong" uniqKey="Luo X" first="Xunrong" last="Luo">Xunrong Luo</name><name sortKey="Luo, Xunrong" sort="Luo, Xunrong" uniqKey="Luo X" first="Xunrong" last="Luo">Xunrong Luo</name><name sortKey="Miller, Stephen D" sort="Miller, Stephen D" uniqKey="Miller S" first="Stephen D" last="Miller">Stephen D. Miller</name><name sortKey="Palani, Nagendra P" sort="Palani, Nagendra P" uniqKey="Palani N" first="Nagendra P" last="Palani">Nagendra P. Palani</name><name sortKey="Ramachandran, Sabarinathan" sort="Ramachandran, Sabarinathan" uniqKey="Ramachandran S" first="Sabarinathan" last="Ramachandran">Sabarinathan Ramachandran</name><name sortKey="Suarez Pinzon, Wilma Lucia" sort="Suarez Pinzon, Wilma Lucia" uniqKey="Suarez Pinzon W" first="Wilma Lucia" last="Suarez-Pinzon">Wilma Lucia Suarez-Pinzon</name><name sortKey="Wilhelm, Joshua J" sort="Wilhelm, Joshua J" uniqKey="Wilhelm J" first="Joshua J" last="Wilhelm">Joshua J. Wilhelm</name><name sortKey="Yang, Amy" sort="Yang, Amy" uniqKey="Yang A" first="Amy" last="Yang">Amy Yang</name><name sortKey="Zhang, Ying" sort="Zhang, Ying" uniqKey="Zhang Y" first="Ying" last="Zhang">Ying Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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