CCL19 (ELC) as an adjuvant for DNA vaccination:: induction of a TH1-type T-cell response and enhancement of antitumor immunity
CCL19 (ELC) as an adjuvant for DNA vaccination:: induction of a TH1-type T-cell response and enhancement of antitumor immunity
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DOI：
10.1038/sj.cgt.7701042
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发表时间：
2007-06-01
影响因子：
6.4
通讯作者：
Pezzutto, A.
中科院分区：
文献类型：
--
作者：
Westermann, J.;Nguyen-Hoai, T.;Pezzutto, A.
肿瘤抗原与免疫调节分子的共表达是DNA疫苗接种的一种策略，旨在增强抗肿瘤免疫反应。eb病毒诱导的分子1配体趋化因子（ELC/CCL19）是一种与趋化因子受体CCR7结合的CC趋化因子。CCR7在成熟树突状细胞（DC）和不同的T细胞和b细胞亚群中表达。CCL19 （ELC）主要表达于次级淋巴器官，在调节DC与T细胞的相遇中起核心作用。我们询问CCL19是否能够在具有同源MCA205 （β -gal）肿瘤细胞的C57BL/6小鼠模型中增强DNA疫苗的免疫原性。小鼠分别于第1天和第15天肌肉注射两次疫苗，第25天皮下注射肿瘤。将质粒DNA (pDNA) （β -gal）和pDNA （CCL19）与pDNA （β -gal）、pDNA （CCL19）、模拟载体和磷酸盐缓冲盐水（PBS）共给药进行比较。CCL19的共表达增强了th1极化免疫应答，显著提高了DNA疫苗的保护作用。免疫组化染色显示pDNA (β -gal) + pDNA （CCL19）免疫小鼠肿瘤组织中CD8+ t细胞浸润增加。我们得出结论，CCL19是一种有吸引力的DNA疫苗佐剂，能够增强抗肿瘤免疫，这种作用部分是由CD8+ t细胞募集增强引起的。
Coexpression of tumor antigens together with immunomodulatory molecules is a strategy in DNA vaccination aiming at an amplification of the antitumor immune response. Epstein-Barr virus-induced-molecule-1-ligand-chemokine (ELC/CCL19) is a CC chemokine that binds to the chemokine receptor CCR7. CCR7 is expressed on mature dendritic cells ( DC) and distinct T- and B-cell subpopulations. CCL19 ( ELC) is mainly expressed in secondary lymphoid organs and plays a central role in regulating the encounters between DC and T cells. We asked whether CCL19 is able to augment immunogenicity of a DNA vaccine in a C57BL/6 mouse model with syngeneic MCA205 (beta-gal) tumor cells. Mice were vaccinated twice intramuscularly on days 1 and 15 and tumor challenge was performed subcutaneously on day 25. Coadministration of plasmid DNA (pDNA) (beta-gal) plus pDNA (CCL19) was compared with pDNA (beta-gal), pDNA (CCL19), mock vector and phosphate-buffered saline ( PBS) alone. Coexpression of CCL19 resulted in enhancement of a Th1-polarized immune response with substantial improvement of the protective effect of the DNA vaccine. Immunohistochemical staining revealed an increased CD8+ T-cell infiltration in the tumor tissue of mice that had been immunized with pDNA (beta-gal) plus pDNA (CCL19). We conclude that CCL19 is an attractive adjuvant for DNA vaccination able to augment antitumor immunity and that this effect is partially caused by enhanced CD8+ T-cell recruitment.