Vandamme Céline
Xicluna Rebecca
Hesnard Leslie
Devaux Marie
Jaulin Nicolas
Guilbaud Mickaël
Le Duff Johanne
Couzinié Célia
Moullier Philippe
Saulquin Xavier
Adjali Oumeya
2021-01-20
<p><strong>Abstract</strong></p>
<p>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. <em>Ex vivo</em> 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.</p>
https://doi.org/10.3389/fimmu.2019.03110
oai:zenodo.org:5584580
Zenodo
https://zenodo.org/communities/upgrade-h2020-project
https://zenodo.org/communities/eu
info:eu-repo/semantics/openAccess
Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/legalcode
Frontiers in Immunology, (2021-01-20)
Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8+ T Cells in Human Donors Allows the Detection of a TEMRA Subpopulation
info:eu-repo/semantics/article