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Titolo:
Retroviral delivery of viral interleukin-10 into myeloid dendritic cells markedly inhibits their allostimulatory activity and promotes the induction of T-cell hyporesponsiveness.
Autore:
Takayama, T; Nishioka, Y; Lu, L; Lotze, MT; Tahara, H; Thomson, AW;
Indirizzi:
Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 pt Surg, Pittsburgh, PA 15213 USA Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA Thomas E Starzl Transplantat Inst Pittsburgh PA USA , Pittsburgh, PA USA UnivAPittsburgh, Med Ctr, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 US Univ Pittsburgh Pittsburgh PA USA 15213 Biochem, Pittsburgh, PA 15213 US
Titolo Testata:
TRANSPLANTATION
fascicolo: 12, volume: 66, anno: 1998,
pagine: 1567 - 1574
SICI:
0041-1337(199812)66:12<1567:RDOVII>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAJOR HISTOCOMPATIBILITY COMPLEX; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; MEDIATED GENE-TRANSFER; MOUSE BONE-MARROW; IN-VIVO; CYTOKINE PRODUCTION; B7 EXPRESSION; IL-10 HOMOLOG; PROGENITORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Thomson, AW Univ Pittsburgh, Med Ctr, Dept Surg, W1544 Biomed Sci Tower,200 Lothrop St, Univ Pittsburgh W1544 Biomed Sci Tower,200 Lothrop St Pittsburgh PA USA 15213
Citazione:
T. Takayama et al., "Retroviral delivery of viral interleukin-10 into myeloid dendritic cells markedly inhibits their allostimulatory activity and promotes the induction of T-cell hyporesponsiveness.", TRANSPLANT, 66(12), 1998, pp. 1567-1574

Abstract

Background Dendritic cells (DC) play critical roles in the initiation and modulation of immune responses and may determine the balance between tolerance and immunity. Viral interleukin-10 (vIL-10), encoded by the Epstein-Barr virus, is highly homologous to the "immunosuppressive" cytokine, mammalian IL-10. It impairs antigen-presenting cell function but lacks certain immunostimulatory properties of mammalian IL-10. We accomplished the following:(1) evaluated the effects of vIL-10 protein on DC phenotype and function, (2) transduced mouse bone marrow-derived DC to express vIL-10, and (3) assessed the impact of transgene expression on DC allostimulatory activity. Methods. DC progenitors propagated from bone marrow of B10 (H2(b)) mice ingranulocyte-macrophage colony-stimulating factor plus IL-4 were repeatedlytransduced by centrifugation, using retroviral supernatant obtained from the BOSC 23 ecotropic packaging cell line. To evaluate transduction efficiency, DC were transduced with the retroviral vector MFG-enhanced green fluorescence protein as a marker gene. Transgene and key cell surface molecule expression were examined by flow cytometry. The level of vIL-10 gene product in the culture supernatant was quantitated by ELISA. DC function was assessed by evaluation of the ability of DC to induce allogeneic (C3H;H2(k)) T-cell proliferation and cytotoxic T lymphocytes in primary mixed leukocyte reactions. Secondary mixed leukocyte reactions were used to test for T-cell hyporesponsiveness. Results. The early addition of vIL-10 protein to cultures inhibited DC maturation and function. vIL-10 gene transfer was achieved with an approximatetransduction efficiency of 35 to 40%. Transduced DC expressed vIL-10 at a level of 40 ng/10(6) cells/48 hr. In comparison with controls, vIL-10-transduced cells showed decreased surface expression of major histocompatibilitycomplex class II and costimulatory molecules, reduced ability to stimulateT-cell proliferation and cytotoxic T lymphocyte generation, and potential to induce alloantigen-specific hyporesponsiveness. Conclusions. DC can be effectively transduced to express vIL-10 and limit their ability to stimulate in vitro. These genetically engineered antigen-presenting cells may have therapeutic potential to inhibit undesired immune responses to allo- or autoantigens.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 20:29:55