Frequency, proliferation, and activation of human memory T cells induced by a nonhuman adenovirus.

Détails

ID Serval
serval:BIB_E7E8F7D321A2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Frequency, proliferation, and activation of human memory T cells induced by a nonhuman adenovirus.
Périodique
Journal of Virology
Auteur(s)
Perreau M., Kremer E.J.
ISSN
0022-538X (Print)
ISSN-L
0022-538X
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
79
Numéro
23
Pages
14595-14605
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Résumé
Multiple human adenovirus (HAd) infections during childhood generate a memory T-cell (T(M)) response, which is the primary defense against HAd-induced morbidity. This cellular memory creates a conundrum for the potential clinical use of HAd-derived vectors: vector-mediated gene transfer is efficient in immunologically naïve mammals but will be compromised by memory immunity when using vectors derived from ubiquitous human pathogens. The potential lack of cellular and humoral memory is one reason we developed vectors from canine adenovirus serotype 2 (CAV-2). Here, we assayed human peripheral blood mononuclear cells for a T(M) response that could be stimulated by CAV-2 virion and individual capsid proteins. We found that less than half of the donors harbored a proliferating T(M) response directed against the CAV-2 virion (versus >85% against HAd5) in spite of a conserved antigenic Adenoviridae epitope in the CAV-2 hexon. When CAV-2 induced proliferation, it was 2.3- to >10-fold lower than HAd5 depending on the assay. The primary proliferating cells appeared to be memory (CD45RO+) CD4+ lymphocytes, differentiated into Th1 gamma interferon-producing cells, with a frequency that was up to 66-fold lower than that obtained for HAd5. We also compared CAV-2 to prototype HAd from five of the six human species and found that CAV-2-induced cellular proliferation was similar to that found with rare HAd serotypes. Individual CAV-2 capsid proteins also induced less proliferation than their HAd5 homologues. Our data suggest that CAV-2 vectors may be safer (i.e., less immunogenic) for gene transfer but are not without a theoretical risk in a subset of potential patients.
Mots-clé
Adenoviridae/genetics, Adenoviridae/immunology, Adenoviruses, Canine/genetics, Antigens, Viral/immunology, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/virology, Capsid Proteins/genetics, Capsid Proteins/immunology, Cell Proliferation, Genetic Vectors, Humans, Immunologic Memory, Lymphocyte Activation
Pubmed
Open Access
Oui
Création de la notice
24/10/2014 13:03
Dernière modification de la notice
20/08/2019 16:10
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