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Titolo:
Differential effects of myeloid dendritic cells retrovirally transduced toexpress mammalian or viral interleukin-10 on cytotoxic T lymphocyte and natural killer cell functions and resistance to tumor growth
Autore:
Takayama, T; Tahara, H; Thomson, AW;
Indirizzi:
Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 at Inst, Pittsburgh, PA 15213 USA Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 pt Surg, Pittsburgh, PA 15213 USA Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 Biochem, Pittsburgh, PA 15213 USA
Titolo Testata:
TRANSPLANTATION
fascicolo: 9, volume: 71, anno: 2001,
pagine: 1334 - 1340
SICI:
0041-1337(20010515)71:9<1334:DEOMDC>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARDIAC ALLOGRAFT SURVIVAL; ANTIGEN-PRESENTING CELLS; MEDIATED GENE-TRANSFER; IN-VITRO; ACTIVATED MACROPHAGES; TOLERANCE INDUCTION; IL-10; HYPORESPONSIVENESS; PROGENITORS; RECIPIENTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Thomson, AW Univ Pittsburgh, Med Ctr, W1544 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA Univ Pittsburgh W1544 Biomed Sci Tower,200 Lothrop St Pittsburgh PA USA 15213
Citazione:
T. Takayama et al., "Differential effects of myeloid dendritic cells retrovirally transduced toexpress mammalian or viral interleukin-10 on cytotoxic T lymphocyte and natural killer cell functions and resistance to tumor growth", TRANSPLANT, 71(9), 2001, pp. 1334-1340

Abstract

Background Genetic engineering of dendritic cells (DC) to express immunosuppressive molecule(s) offers potential for therapy of allograft rejection and autoimmune disease, Viral (v) interleukin (IL)-10, encoded by the Epstein-Barr virus, is highly homologous to mammalian (m) IL-10, but lacks certain of its T-cell stimulatory activities. Our aim was to evaluate and comparethe influence of vIL-10 and mIL-10 gene transfer on the T-cell and naturalkiller (WR) cell stimulatory activity of DC, and their impact on the growth of transplantable tumors,Methods, Myeloid DC progenitors, propagated from the bone marrow of C57BL/6J (H2(b)) mice in granulocyte-macrophage colony-stimulating factor + IL-4,were transduced using retroviral supernatant from the BOSC ecotropic packaging cell line. The function of the IL-IO gene-modified DC was assessed by examining their ability to induce naive allogeneic T-cell proliferation andcytotoxic T lymphocyte (CTL) generation. MCA205 (H2b) sarcoma cells mixed with either vIL-10-, mIL-10-, or Zeo (control gene)-transduced DC were inoculated intradermally into C57BL/6J (syngeneic) or BALB/cJ (H2(d)) (allogeneic) recipients, which were monitored for tumor growth, The role of specifichost effector cell populations in tumor resistance was determined by antibody depletion. Results, Compared with control gene-modified DC, both vIL-10- and mIL-10-transduced DC, which secreted the transgene product, showed reduced surface expression of MHC class II and costimulatory molecules, and impaired ability to induce T-cell proliferation. vIL-10-transduced DC were also inhibited with respect to CTL induction but did not affect the generation of NE; cells. By contrast, mIL-10-transduced DC augmented CTL generation and NH cell activity. in the tumor transplant model, vIL-10-transduced DC enhanced tumorgrowth both in syngeneic and allogeneic hosts, whereas mIL-10-transduced cells inhibited tumor development, Depletion of CD4(+) or CDS' T cells or NKcells in mice given mIL-10-transduced DC reversed this therapeutic effect. Conclusion. mIL-10 gene-modified myeloid DC promote CTL and NK cell-mediated responses and inhibit tumor growth. By contrast, vIl-10-engineered DC, which elicit diminished CTE responses and do not promote NK cell activity, seem to have therapeutic potential for inhibition of T cell-mediated immunity.

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Documento generato il 04/07/20 alle ore 12:26:29