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Titolo:
Viral IL-10 gene transfer inhibits DTH responses to soluble antigens: Evidence for involvement of genetically modified dendritic cells and macrophages
Autore:
Whalen, JD; Thomson, AW; Lu, L; Robbins, PD; Evans, CH;
Indirizzi:
Harvard Univ, Sch Med, Ctr Mol Orthopaed, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Ctr Mol Orthopaed, Boston, MA 02115 USA Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15312 USA Univ Pittsburgh Pittsburgh PA USA 15312 Biochem, Pittsburgh, PA 15312 USA Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15312 USA Univ Pittsburgh Pittsburgh PA USA 15312 at Inst, Pittsburgh, PA 15312 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 4, anno: 2001,
pagine: 543 - 550
SICI:
1525-0016(200112)4:6<543:VIGTID>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
DELAYED-TYPE HYPERSENSITIVITY; CYTOKINE PRODUCTION; IN-VIVO; EXPERIMENTAL ARTHRITIS; PRESENTING CELL; RABBIT KNEES; INTERLEUKIN-10; TH1; SUPPRESSION; MODULATION;
Keywords:
arthritis; dendritic cell; macrophage; antigen presentation; autoimmunity; adoptive transfer; lymphocyte; immunomodulation; contralateral effect;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Evans, CH Harvard Univ, Sch Med, Ctr Mol Orthopaed, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 rthopaed, Boston, MA 02115 USA
Citazione:
J.D. Whalen et al., "Viral IL-10 gene transfer inhibits DTH responses to soluble antigens: Evidence for involvement of genetically modified dendritic cells and macrophages", MOL THER, 4(6), 2001, pp. 543-550

Abstract

Expression of the viral interleukin-10 (vIL-10) gene within one joint of an animal with polyarticular, inflammatory arthritis suppresses disease in both treated and untreated joints (the "contralateral effect"). We used a mouse delayed-type hypersensitivity (DTH) model to investigate this phenomenon. Adenoviral delivery of the vIL-10 gene suppressed DTH reactions in injected and contralateral paws. T lymphocytes recovered from immunized mice injected with the adenoviral vector (ad-vIL-10) were unable to transfer the DTH response, but were not inhibitory. Peritoneal exudate cells recovered from mice injected intraperitoneally with ad-vIL-10 inhibited DTH reactions inrecipient mice, but only when the donor mice had been sensitized to the antigen used to incite the DTH response. Dendritic cells (DCs) recovered fromthe draining lymph nodes of mice injected with ad-vIL-10 behaved similarly. Bone-marrow-derived DCs cultured ex vivo with ad-vIL-10 or recombinant mouse IL-10 also suppressed DTH reactions by adoptive transfer when pulsed with the inciting antigen. Collectively, these data suggest a mechanism for the contralateral effect in which genetically modified macrophages and DCs present antigen in the context of high, local concentrations of vIL-10, thereby generating unresponsive T lymphocytes. These findings suggest new ways in which to treat immune-driven diseases by gene and cell therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/05/20 alle ore 14:57:30