January 20, 2021 Journal article Open Access

Vandamme Céline; Xicluna Rebecca; Hesnard Leslie; Devaux Marie; Jaulin Nicolas; Guilbaud Mickaël; Le Duff Johanne; Couzinié Célia; Moullier Philippe; Saulquin Xavier; Adjali Oumeya

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  <identifier identifierType="URL">https://zenodo.org/record/5584580</identifier>
  <creators>
    <creator>
      <creatorName>Vandamme Céline</creatorName>
      <affiliation>INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Xicluna Rebecca</creatorName>
      <affiliation>INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Hesnard Leslie</creatorName>
      <affiliation>CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Devaux Marie</creatorName>
      <affiliation>INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Jaulin Nicolas</creatorName>
      <affiliation>INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Guilbaud Mickaël</creatorName>
      <affiliation>INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Le Duff Johanne</creatorName>
      <affiliation>INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Couzinié Célia</creatorName>
      <affiliation>INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Moullier Philippe</creatorName>
      <affiliation>INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Saulquin Xavier</creatorName>
      <affiliation>CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France</affiliation>
    </creator>
    <creator>
      <creatorName>Adjali Oumeya</creatorName>
      <affiliation>INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8+ T Cells in Human Donors Allows the Detection of a TEMRA Subpopulation</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2021</publicationYear>
  <dates>
    <date dateType="Issued">2021-01-20</date>
  </dates>
  <resourceType resourceTypeGeneral="JournalArticle"/>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/5584580</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.3389/fimmu.2019.03110</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/upgrade-h2020-project</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;&lt;strong&gt;Abstract&lt;/strong&gt;&lt;/p&gt;

&lt;p&gt;Pre-existing immunity to AAV capsid may compromise the safety and efficiency of rAAV-mediated gene transfer in patients. Anti-capsid cytotoxic immune responses have proven to be a challenge to characterize because of the scarcity of circulating AAV-specific CD8+&amp;nbsp;T lymphocytes which can seldom be detected with conventional flow cytometry or ELISpot assays. Here, we used fluorescent MHC class I tetramers combined with magnetic enrichment to detect and phenotype AAV8-specific CD8+&amp;nbsp;T cells in human PBMCs without prior amplification. We showed that all healthy individuals tested carried a pool of AAV8-specific CD8+&amp;nbsp;T cells with a CD45RA+CCR7&amp;minus;&amp;nbsp;terminally-differentiated effector memory cell (TEMRA) fraction.&amp;nbsp;&lt;em&gt;Ex vivo&lt;/em&gt;&amp;nbsp;frequencies of total AAV-specific CD8+&amp;nbsp;T cells were not predictive of IFN&amp;gamma; ELISpot responses but interestingly we evidenced a correlation between the proportion of TEMRA&amp;nbsp;cells and IFN&amp;gamma; ELISpot positive responses. TEMRA&amp;nbsp;cells may then play a role in recombinant AAV-mediated cytotoxicity in patients with preexisting immunity. Overall, our results encourage the development of new methods combining increased detection sensitivity of AAV-specific T cells and their poly-functional assessment to better characterize and monitor AAV capsid-specific cellular immune responses in the perspective of rAAV-mediated clinical trials.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/100010661</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/825825/">825825</awardNumber>
      <awardTitle>Unlocking Precision Gene Therapy</awardTitle>
    </fundingReference>
  </fundingReferences>
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