Generation and Characterization of Alloantigen-Specific Regulatory T Cells For Clinical Transplant Tolerance.
Identifieur interne : 000600 ( Main/Exploration ); précédent : 000599; suivant : 000601Generation and Characterization of Alloantigen-Specific Regulatory T Cells For Clinical Transplant Tolerance.
Auteurs : James M. Mathew [États-Unis] ; Jessica H. Voss [États-Unis] ; Scott T. Mcewen [États-Unis] ; Iwona Konieczna [États-Unis] ; Arjun Chakraborty [États-Unis] ; Xuemei Huang [États-Unis] ; Jie He [États-Unis] ; Lorenzo Gallon [États-Unis] ; Richard S. Kornbluth [États-Unis] ; Joseph R. Leventhal [États-Unis]Source :
- Scientific reports [ 2045-2322 ] ; 2018.
Descripteurs français
- KwdFr :
- Activation des lymphocytes (immunologie), Cellules présentatrices d'antigène (immunologie), Cellules présentatrices d'antigène (métabolisme), Facteurs de transcription Forkhead (métabolisme), Humains (MeSH), Immunologie en transplantation (MeSH), Isoantigènes (immunologie), Lymphocytes B (immunologie), Lymphocytes B (métabolisme), Lymphocytes T régulateurs (immunologie), Lymphocytes T régulateurs (métabolisme), Marqueurs biologiques (MeSH), Méthylation (MeSH), Récepteurs aux antigènes des cellules T (MeSH), Sous-populations de lymphocytes T (immunologie), Sous-populations de lymphocytes T (métabolisme), Test de culture lymphocytaire mixte (MeSH), Tolérance à la transplantation (immunologie), Transplantation d'organe (MeSH).
- MESH :
- immunologie : Activation des lymphocytes, Cellules présentatrices d'antigène, Isoantigènes, Lymphocytes B, Lymphocytes T régulateurs, Sous-populations de lymphocytes T, Tolérance à la transplantation.
- métabolisme : Cellules présentatrices d'antigène, Facteurs de transcription Forkhead, Lymphocytes B, Lymphocytes T régulateurs, Sous-populations de lymphocytes T.
- Humains, Immunologie en transplantation, Marqueurs biologiques, Méthylation, Récepteurs aux antigènes des cellules T, Test de culture lymphocytaire mixte, Transplantation d'organe.
English descriptors
- KwdEn :
- Antigen-Presenting Cells (immunology), Antigen-Presenting Cells (metabolism), B-Lymphocytes (immunology), B-Lymphocytes (metabolism), Biomarkers (MeSH), Forkhead Transcription Factors (metabolism), Humans (MeSH), Isoantigens (immunology), Lymphocyte Activation (immunology), Lymphocyte Culture Test, Mixed (MeSH), Methylation (MeSH), Organ Transplantation (MeSH), Receptors, Antigen, T-Cell (MeSH), T-Lymphocyte Subsets (immunology), T-Lymphocyte Subsets (metabolism), T-Lymphocytes, Regulatory (immunology), T-Lymphocytes, Regulatory (metabolism), Transplantation Immunology (MeSH), Transplantation Tolerance (immunology).
- MESH :
- chemical , immunology : Isoantigens.
- chemical , metabolism : Forkhead Transcription Factors.
- chemical : Biomarkers, Receptors, Antigen, T-Cell.
- immunology : Antigen-Presenting Cells, B-Lymphocytes, Lymphocyte Activation, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Transplantation Tolerance.
- metabolism : Antigen-Presenting Cells, B-Lymphocytes, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory.
- Humans, Lymphocyte Culture Test, Mixed, Methylation, Organ Transplantation, Transplantation Immunology.
Abstract
Donor-specific CD4+CD127-CD25+FOXP3+ regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination. Purified allogeneic "recipient" CD4+CD25+ Tregs were stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2, TGFβ and sirolimus (SRL). Tregs were further amplified by polyclonal stimulation with anti-CD3/CD28 beads on day 14 without SRL, and harvested on day 21, with extrapolated fold expansion into the thousands. The expanded AgTregs maintained expression of classical Treg markers including demethylation of the Treg-specific demethylated region (CNS2) and also displayed constricted TcR repertoire. We observed AgTregs more potently inhibited MLR than polyclonally expanded Tregs and generated new Tregs in autologous responder cells (a measure of infectious tolerance). Thus, an optimized and more clinically applicable protocol for the expansion of donor-specific Tregs has been developed.
DOI: 10.1038/s41598-018-19621-6
PubMed: 29348660
PubMed Central: PMC5773708
Affiliations:
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Mathew</name><affiliation wicri:level="2"><nlm:affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. james-mathew@northwestern.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. james-mathew@northwestern.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Voss, Jessica H" sort="Voss, Jessica H" uniqKey="Voss J" first="Jessica H" last="Voss">Jessica H. Voss</name><affiliation wicri:level="2"><nlm:affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Mcewen, Scott T" sort="Mcewen, Scott T" uniqKey="Mcewen S" first="Scott T" last="Mcewen">Scott T. Mcewen</name><affiliation wicri:level="2"><nlm:affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Ann & Robert H. Lurie Children's Hospital, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Ann & Robert H. Lurie Children's Hospital, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Konieczna, Iwona" sort="Konieczna, Iwona" uniqKey="Konieczna I" first="Iwona" last="Konieczna">Iwona Konieczna</name><affiliation wicri:level="2"><nlm:affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Chakraborty, Arjun" sort="Chakraborty, Arjun" uniqKey="Chakraborty A" first="Arjun" last="Chakraborty">Arjun Chakraborty</name><affiliation wicri:level="2"><nlm:affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Huang, Xuemei" sort="Huang, Xuemei" uniqKey="Huang X" first="Xuemei" last="Huang">Xuemei Huang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="He, Jie" sort="He, Jie" uniqKey="He J" first="Jie" last="He">Jie He</name><affiliation wicri:level="2"><nlm:affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Gallon, Lorenzo" sort="Gallon, Lorenzo" uniqKey="Gallon L" first="Lorenzo" last="Gallon">Lorenzo Gallon</name><affiliation wicri:level="2"><nlm:affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine- Nephrology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine- Nephrology, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Kornbluth, Richard S" sort="Kornbluth, Richard S" uniqKey="Kornbluth R" first="Richard S" last="Kornbluth">Richard S. Kornbluth</name><affiliation wicri:level="2"><nlm:affiliation>Multimeric Biotherapeutics, Inc., La Jolla, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Multimeric Biotherapeutics, Inc., La Jolla, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Leventhal, Joseph R" sort="Leventhal, Joseph R" uniqKey="Leventhal J" first="Joseph R" last="Leventhal">Joseph R. Leventhal</name><affiliation wicri:level="2"><nlm:affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antigen-Presenting Cells (immunology)</term><term>Antigen-Presenting Cells (metabolism)</term><term>B-Lymphocytes (immunology)</term><term>B-Lymphocytes (metabolism)</term><term>Biomarkers (MeSH)</term><term>Forkhead Transcription Factors (metabolism)</term><term>Humans (MeSH)</term><term>Isoantigens (immunology)</term><term>Lymphocyte Activation (immunology)</term><term>Lymphocyte Culture Test, Mixed (MeSH)</term><term>Methylation (MeSH)</term><term>Organ Transplantation (MeSH)</term><term>Receptors, Antigen, T-Cell (MeSH)</term><term>T-Lymphocyte Subsets (immunology)</term><term>T-Lymphocyte Subsets (metabolism)</term><term>T-Lymphocytes, Regulatory (immunology)</term><term>T-Lymphocytes, Regulatory (metabolism)</term><term>Transplantation Immunology (MeSH)</term><term>Transplantation Tolerance (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes (immunologie)</term><term>Cellules présentatrices d'antigène (immunologie)</term><term>Cellules présentatrices d'antigène (métabolisme)</term><term>Facteurs de transcription Forkhead (métabolisme)</term><term>Humains (MeSH)</term><term>Immunologie en transplantation (MeSH)</term><term>Isoantigènes (immunologie)</term><term>Lymphocytes B (immunologie)</term><term>Lymphocytes B (métabolisme)</term><term>Lymphocytes T régulateurs (immunologie)</term><term>Lymphocytes T régulateurs (métabolisme)</term><term>Marqueurs biologiques (MeSH)</term><term>Méthylation (MeSH)</term><term>Récepteurs aux antigènes des cellules T (MeSH)</term><term>Sous-populations de lymphocytes T (immunologie)</term><term>Sous-populations de lymphocytes T (métabolisme)</term><term>Test de culture lymphocytaire mixte (MeSH)</term><term>Tolérance à la transplantation (immunologie)</term><term>Transplantation d'organe (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Isoantigens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Forkhead Transcription Factors</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Biomarkers</term><term>Receptors, Antigen, T-Cell</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Activation des lymphocytes</term><term>Cellules présentatrices d'antigène</term><term>Isoantigènes</term><term>Lymphocytes B</term><term>Lymphocytes T régulateurs</term><term>Sous-populations de lymphocytes T</term><term>Tolérance à la transplantation</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Antigen-Presenting Cells</term><term>B-Lymphocytes</term><term>Lymphocyte Activation</term><term>T-Lymphocyte Subsets</term><term>T-Lymphocytes, Regulatory</term><term>Transplantation Tolerance</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Antigen-Presenting Cells</term><term>B-Lymphocytes</term><term>T-Lymphocyte Subsets</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules présentatrices d'antigène</term><term>Facteurs de transcription Forkhead</term><term>Lymphocytes B</term><term>Lymphocytes T régulateurs</term><term>Sous-populations de lymphocytes T</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Lymphocyte Culture Test, Mixed</term><term>Methylation</term><term>Organ Transplantation</term><term>Transplantation Immunology</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Immunologie en transplantation</term><term>Marqueurs biologiques</term><term>Méthylation</term><term>Récepteurs aux antigènes des cellules T</term><term>Test de culture lymphocytaire mixte</term><term>Transplantation d'organe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Donor-specific CD4<sup>+</sup>CD127<sup>-</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination. Purified allogeneic "recipient" CD4<sup>+</sup>CD25<sup>+</sup> Tregs were stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2, TGFβ and sirolimus (SRL). Tregs were further amplified by polyclonal stimulation with anti-CD3/CD28 beads on day 14 without SRL, and harvested on day 21, with extrapolated fold expansion into the thousands. The expanded AgTregs maintained expression of classical Treg markers including demethylation of the Treg-specific demethylated region (CNS2) and also displayed constricted TcR repertoire. We observed AgTregs more potently inhibited MLR than polyclonally expanded Tregs and generated new Tregs in autologous responder cells (a measure of infectious tolerance). Thus, an optimized and more clinically applicable protocol for the expansion of donor-specific Tregs has been developed.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29348660</PMID><DateCompleted><Year>2018</Year><Month>11</Month><Day>27</Day></DateCompleted><DateRevised><Year>2019</Year><Month>01</Month><Day>18</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><Issue>1</Issue><PubDate><Year>2018</Year><Month>01</Month><Day>18</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>Generation and Characterization of Alloantigen-Specific Regulatory T Cells For Clinical Transplant Tolerance.</ArticleTitle><Pagination><MedlinePgn>1136</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41598-018-19621-6</ELocationID><Abstract><AbstractText>Donor-specific CD4<sup>+</sup>CD127<sup>-</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination. Purified allogeneic "recipient" CD4<sup>+</sup>CD25<sup>+</sup> Tregs were stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2, TGFβ and sirolimus (SRL). Tregs were further amplified by polyclonal stimulation with anti-CD3/CD28 beads on day 14 without SRL, and harvested on day 21, with extrapolated fold expansion into the thousands. The expanded AgTregs maintained expression of classical Treg markers including demethylation of the Treg-specific demethylated region (CNS2) and also displayed constricted TcR repertoire. We observed AgTregs more potently inhibited MLR than polyclonally expanded Tregs and generated new Tregs in autologous responder cells (a measure of infectious tolerance). Thus, an optimized and more clinically applicable protocol for the expansion of donor-specific Tregs has been developed.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mathew</LastName><ForeName>James M</ForeName><Initials>JM</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-5667-750X</Identifier><AffiliationInfo><Affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. james-mathew@northwestern.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. james-mathew@northwestern.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Voss</LastName><ForeName>Jessica H</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McEwen</LastName><ForeName>Scott T</ForeName><Initials>ST</Initials><AffiliationInfo><Affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Ann & Robert H. Lurie Children's Hospital, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Konieczna</LastName><ForeName>Iwona</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chakraborty</LastName><ForeName>Arjun</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Xuemei</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>He</LastName><ForeName>Jie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gallon</LastName><ForeName>Lorenzo</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine- Nephrology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kornbluth</LastName><ForeName>Richard S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Multimeric Biotherapeutics, Inc., La Jolla, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leventhal</LastName><ForeName>Joseph R</ForeName><Initials>JR</Initials><AffiliationInfo><Affiliation>Department of Surgery - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>01</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci Rep</MedlineTA><NlmUniqueID>101563288</NlmUniqueID><ISSNLinking>2045-2322</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C418974">FOXP3 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051858">Forkhead Transcription Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007519">Isoantigens</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011948">Receptors, Antigen, T-Cell</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000938" MajorTopicYN="N">Antigen-Presenting Cells</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001402" MajorTopicYN="N">B-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015415" MajorTopicYN="N">Biomarkers</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051858" MajorTopicYN="N">Forkhead Transcription Factors</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007519" MajorTopicYN="N">Isoantigens</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007959" MajorTopicYN="N">Lymphocyte Culture Test, Mixed</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008745" MajorTopicYN="N">Methylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016377" MajorTopicYN="N">Organ Transplantation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011948" MajorTopicYN="N">Receptors, Antigen, T-Cell</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016176" MajorTopicYN="N">T-Lymphocyte Subsets</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050378" MajorTopicYN="N">T-Lymphocytes, Regulatory</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014181" MajorTopicYN="N">Transplantation Immunology</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D023001" MajorTopicYN="N">Transplantation Tolerance</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>06</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>01</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>1</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>1</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>11</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29348660</ArticleId><ArticleId IdType="doi">10.1038/s41598-018-19621-6</ArticleId><ArticleId 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Mathew</name></region><name sortKey="Chakraborty, Arjun" sort="Chakraborty, Arjun" uniqKey="Chakraborty A" first="Arjun" last="Chakraborty">Arjun Chakraborty</name><name sortKey="Gallon, Lorenzo" sort="Gallon, Lorenzo" uniqKey="Gallon L" first="Lorenzo" last="Gallon">Lorenzo Gallon</name><name sortKey="Gallon, Lorenzo" sort="Gallon, Lorenzo" uniqKey="Gallon L" first="Lorenzo" last="Gallon">Lorenzo Gallon</name><name sortKey="He, Jie" sort="He, Jie" uniqKey="He J" first="Jie" last="He">Jie He</name><name sortKey="Huang, Xuemei" sort="Huang, Xuemei" uniqKey="Huang X" first="Xuemei" last="Huang">Xuemei Huang</name><name sortKey="Konieczna, Iwona" sort="Konieczna, Iwona" uniqKey="Konieczna I" first="Iwona" last="Konieczna">Iwona Konieczna</name><name sortKey="Kornbluth, Richard S" sort="Kornbluth, Richard S" uniqKey="Kornbluth R" first="Richard S" last="Kornbluth">Richard S. Kornbluth</name><name sortKey="Leventhal, Joseph R" sort="Leventhal, Joseph R" uniqKey="Leventhal J" first="Joseph R" last="Leventhal">Joseph R. Leventhal</name><name sortKey="Mathew, James M" sort="Mathew, James M" uniqKey="Mathew J" first="James M" last="Mathew">James M. Mathew</name><name sortKey="Mcewen, Scott T" sort="Mcewen, Scott T" uniqKey="Mcewen S" first="Scott T" last="Mcewen">Scott T. Mcewen</name><name sortKey="Mcewen, Scott T" sort="Mcewen, Scott T" uniqKey="Mcewen S" first="Scott T" last="Mcewen">Scott T. Mcewen</name><name sortKey="Voss, Jessica H" sort="Voss, Jessica H" uniqKey="Voss J" first="Jessica H" last="Voss">Jessica H. Voss</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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