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Titolo:
F;actors influencing cross-presentation of non-self antigens expressed from recombinant adeno-associated virus vectors
Autore:
Sarukhan, A; Soudais, C; Danos, O; Jooss, K;
Indirizzi:
Genethon 3, CNRS URA 1923, F-91002 Evry, France Genethon 3 Evry France F-91002 on 3, CNRS URA 1923, F-91002 Evry, France Inst Necker, INSERM 345, Paris, France Inst Necker Paris FranceInst Necker, INSERM 345, Paris, France
Titolo Testata:
JOURNAL OF GENE MEDICINE
fascicolo: 3, volume: 3, anno: 2001,
pagine: 260 - 270
SICI:
1099-498X(200105/06)3:3<260:FICONA>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYTOTOXIC T-LYMPHOCYTES; DIRECTED GENE-THERAPY; COAGULATION FACTOR-IX; ADENOASSOCIATED VIRUS; DENDRITIC CELLS; IN-VIVO; PRESENTING FUNCTION; LENTIVIRUS VECTOR; IMMUNE-RESPONSE; FACTOR-VIII;
Keywords:
recombinant adeno-associated virus; immunogenicity; cross-presentation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Jooss, K Genethon 3, CNRS URA 1923, 1 Rue Int, F-91002 Evry, France Genethon 3 1 Rue Int Evry France F-91002 t, F-91002 Evry, France
Citazione:
A. Sarukhan et al., "F;actors influencing cross-presentation of non-self antigens expressed from recombinant adeno-associated virus vectors", J GENE MED, 3(3), 2001, pp. 260-270

Abstract

Background We have previously demonstrated that recombinant adenoassociated virus vectors expressing the influenza virus hemagglutinin (rAAV-HA) in skeletal muscle results in T-cell priming and muscle fiber destruction due to cross-presentation of HA by dendritic cells (DC). Based on controversial observations concerning the stability of non-self proteins expressed from rAAV vectors it is important to understand the factors influencing cross-presentation of transgene products following rAAV mediated gene transfer, in order to be able to use this vector safely in the clinic. Methods In order to understand the factors influencing in vivo cross-presentation of non-self proteins, we have retargeted the immunogenic lacZ protein in the context of rAAV from the cytoplasm to the cell surface and studied the activation of LacZ specific immune responses following intramuscular mediated gene transfer. In addition, using tools available for studying in vitro HA-specific T-cell activation, our aim was to identify the cell typesinvolved in class I and class II restricted cross-presentation as well as the nature of the cross-presented material. Results By retargeting the lacZ protein in the context of rAAV to the cellmembrane, we found that one of the factors influencing the efficiency of cross-presentation of non-self antigens is the localization of the transgeneproduct within the target cells. Following rAAV-LacZ mediated gene transfer to the muscle we demonstrated that the membrane-bound form of LacZ resulted in target cell destruction, which is in stark contrast to the stability observed with rAAV-LacZ vectors expressing the cytoplasmic form of LacZ. Using an in vitro assay, we were able to show that dendritic cells (DC) in addition to B-cells cross-presented HA to class II restricted T-ceIls whereasonly the former were able to activate class I restricted CD8 + T-cells. High-dose antigens were needed for efficient class I restricted T-cell priming, whereas class II restricted T-fells were activated by less antigen. Conclusion The present results indicate that immune responses to non-self antigens expressed from rAAV Vectors depend on the accessibility of such antigens to different local antigen-presenting cells. Copyright (C) 2001 JohnWiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 00:11:00