Recombinant adenovirus-transduced human dendritic cells engineered to secrete interleukin-10 (IL-10) suppress Th1-type responses while selectively activating IL-10-producing CD4+ T cells

被引:11
作者
Rea, D
Laface, D
Hutchins, B
Kwappenberg, K
Melief, CJM
Hoeben, RC
Offringa, R
机构
[1] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2333 ZA Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2333 ZA Leiden, Netherlands
[3] Canji Inc, San Diego, CA USA
关键词
interleukin-10; dendritic cell; adenovirus; CD4(+) T helper cell; tolerance;
D O I
10.1016/j.humimm.2004.08.185
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Recombinant adenoviruses (rAd) are efficient tools for genetic modification of human dendritic cells (DC) in vitro. Infection of DCs by rAd encoding beta-galactosidase (betagal) results in partial maturation of DCs, as witnessed by the upregulation of major histocompatibility complex and costimulatory molecules. Accordingly, these DCs are more potent stimulators of Th1-type proliferative responses. We now demonstrate that infection of immature DCs with rAd encoding human interleukin (IL)-10 results in the secretion by the DCs of large amounts of IL-10, while not affecting expression of activation markers indicative of partial DC maturation. In contrast to rAd-betagal-infected DCs, rAdIL-10-infected DCs are very poor stimulators of monoclonal and polyclonal Th1-type responses. Instead, stimulation of nonpolarized CD4(+) T-cell cultures with rAdIL-10-infected DCs selectively activates and expands an IL-10-producing CD4(+) T-cell subset capable of suppressing Th1 responses in vitro. Our data argue that rAd-infected human DCs genetically engineered to produce IL-10 may be exploited for the modulation of harmful Th1-type responses in transplantation and autoimmune diseases. Human Immunology 65, (C) American Society for Histocompatibility and Immunogenetics, 2004. Published by Elsevier Inc.
引用
收藏
页码:1344 / 1355
页数:12
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