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Journal article Open Access

Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8+ T Cells in Human Donors Allows the Detection of a TEMRA Subpopulation

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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<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Vandamme Céline</dc:creator>
  <dc:creator>Xicluna Rebecca</dc:creator>
  <dc:creator>Hesnard Leslie</dc:creator>
  <dc:creator>Devaux Marie</dc:creator>
  <dc:creator>Jaulin Nicolas</dc:creator>
  <dc:creator>Guilbaud Mickaël</dc:creator>
  <dc:creator>Le Duff Johanne</dc:creator>
  <dc:creator>Couzinié Célia</dc:creator>
  <dc:creator>Moullier Philippe</dc:creator>
  <dc:creator>Saulquin Xavier</dc:creator>
  <dc:creator>Adjali Oumeya</dc:creator>

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+ 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+ T cells in human PBMCs without prior amplification. We showed that all healthy individuals tested carried a pool of AAV8-specific CD8+ T cells with a CD45RA+CCR7− terminally-differentiated effector memory cell (TEMRA) fraction. Ex vivo frequencies of total AAV-specific CD8+ T cells were not predictive of IFNγ ELISpot responses but interestingly we evidenced a correlation between the proportion of TEMRA cells and IFNγ ELISpot positive responses. TEMRA 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.</dc:description>
  <dc:source>Frontiers in Immunology</dc:source>
  <dc:title>Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8+ T Cells in Human Donors Allows the Detection of a TEMRA Subpopulation</dc:title>
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