Contrasting effects of myeloid dendritic cells transduced with an adenoviral vector encoding interleukin-10 on organ allograft and tumour rejection

被引:22
作者
Lee, WC
Qiani, S
Wan, Y
Li, W
Xing, Z
Gauldie, J
Fung, JJ
Thomson, AW
Lu, L
机构
[1] Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA
[3] McMaster Univ, Dept Pathol & Biol, Hamilton, ON, Canada
关键词
D O I
10.1046/j.1365-2567.2000.00096.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mouse bone marrow-derived myeloid dendritic cells (DC) propagated in granulocyte-macrophage colony-stimulating factor and transforming growth factor-beta(1) (TGF-beta(1)) (so-called 'TGF-beta DC') are phenotypically immature, and prolong allograft survival. Interleukin-10 (IL-10) has been shown to inhibit the maturation of DC by down-regulating surface major histocompatibility complex (MHC) class II, co-stimulatory and adhesion molecule expression. Genetic engineering of TGF-beta DC to overexpress IL-10 might enhance their tolerogenic potential. In this study, adenoviral (Ad) vectors encoding the mouse IL-10 gene were transduced into B10 (H2(b)) TGF-beta DC. Transduction with Ad-IL-10 at a multiplicity of infection (MOI) of 50-100 resulted in a modest reduction in the incidence of DC expressing surface MHC class II, CD40, CD80 and CD86. Paradoxically, Ad-IL-10 transduction enhanced the allostimulatory activity of DC in mixed leucocyte reactions and cytotoxic T lymphocyte assays, and increased their natural killer cell stimulatory activity. Systemic injection of normal C3H recipients with Ad-IL-10-transduced B10-DC 7 days before organ transplantation, exacerbated heart graft rejection and augmented circulating anti-donor alloantibody titres. Contrasting effects were observed in relation to tumour growth. All mice preimmunized with Ad-IL-10-transduced, tumour antigen (B16F10)-pulsed DC developed palpable tumours, associated with significant inhibition of splenic anti-tumour cytotoxic T lymphocyte generation. Animals pretreated with control Ad-LacZ-transduced, B16F10-pulsed DC however, remained tumour free. These findings are consistent with the multifunctional immunomodulatory properties of mammalian IL-10.
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页码:233 / 241
页数:9
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