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Titolo:
Immune evasion by muscle-specific gene expression in dystrophic muscle
Autore:
Hartigan-OConnor, D; Kirk, CJ; Crawford, R; Mule, JJ; Chamberlain, JS;
Indirizzi:
Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 , Dept Neurol, Seattle, WA 98195 USA Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 , Dept Surg, Ann Arbor, MI 48109 USA Univ Michigan, Med Ctr, Ctr Comprehens Canc, Tumor Immunol Program, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 nol Program, Ann Arbor, MI 48109 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 4, anno: 2001,
pagine: 525 - 533
SICI:
1525-0016(200112)4:6<525:IEBMGE>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
MONOCLONAL-ANTIBODY ANALYSIS; DUCHENNE MUSCULAR-DYSTROPHY; MEDIATED CYTO-TOXICITY; MDX MOUSE; MONONUCLEAR-CELLS; ADENOVIRUS VECTORS; DEFICIENT MUSCLE; DENDRITIC CELLS; DNA-POLYMERASE; IN-VIVO;
Keywords:
dystrophy; dystrophin; gene therapy; adenovirus; antigen-presenting; cross-presentation; cross-priming;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Chamberlain, JS Univ Washington, Sch Med, Dept Neurol, HSB Room K243,Box 357720, Seattle, WA 98195 USA Univ Washington HSB Room K243,Box 357720 Seattle WA USA 98195
Citazione:
D. Hartigan-O'Connor et al., "Immune evasion by muscle-specific gene expression in dystrophic muscle", MOL THER, 4(6), 2001, pp. 525-533

Abstract

Muscle tissue from Duchenne muscular dystrophy patients and the Dmd(mdx/mdx) (hereafter referred to as mdx) mouse is characterized by an abundance ofnecrotic myofibers and infiltrating macrophages. Both features may provideadditional stimulus to the immune response directed against novel antigens, such as those delivered by gene therapy vectors. It has previously been shown that the immune evasion achieved by adeno-associated virus in healthy muscle fails in one model of muscular dystrophy. Here, we examined the immune response to adenoviral vectors and their transgenes in normal and mdx mice. We found that mdx mouse muscles contain 20 times more macrophages and 7times more dendritic cells than healthy muscles. This higher professional antigen-presenting cell content results in a stronger immune response to antigens that can be directly presented by those cells, including viral antigens and constitutively expressed transgene products. However, we did not detect a significant immune response to beta -galactosidase expressed specifically in muscle, even at high expression levels. This result suggests that cross-presentation is not more effective in mdx mouse muscle, and that targeted vectors and tissue-specific promoters may be useful tools for evasion of the immune response in dystrophic muscle.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 07:34:28