Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8 + T Cells in Human Donors Allows the Detection of a T EMRA Subpopulation
In: ISSN: 1664-3224, 2020
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academicJournal
Zugriff:
International audience ; 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 (T EMRA) 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 T EMRA cells and IFNγ ELISpot positive responses. T EMRA 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.
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Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8 + T Cells in Human Donors Allows the Detection of a T EMRA Subpopulation
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Autor/in / Beteiligte Person: | Vandamme, Celine ; Xicluna, Rebecca ; Hesnard, Leslie ; Devaux, Marie ; Jaulin, Nicolas ; Guilbaud, Mickaël ; Le Duff, Johanne ; Couzinié, Célia ; Moullier, Philippe ; Saulquin, Xavier ; Adjali, Oumeya ; Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université de Nantes (UN) ; Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1) ; Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA) ; Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010) |
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Zeitschrift: | ISSN: 1664-3224, 2020 |
Veröffentlichung: | HAL CCSD ; Frontiers, 2020 |
Medientyp: | academicJournal |
DOI: | 10.3389/fimmu.2019.03110 |
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