Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens

Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens
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DOI:
10.4049/jimmunol.167.11.6644
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发表时间:
2001-12-01
影响因子:
4.4
通讯作者:
Kwak, LW
Kwak, LW
中科院分区:
医学2区
文献类型:
--
作者:
Biragyn, A;Surenhu, M;Kwak, LW

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趋化因子受体在未成熟和成熟树突状细胞(DQ.在此,我们首次证明鼠抗微生物肽β-防御素2和3与鼠CCR 6结合,类似于炎性趋化因子巨噬细胞-炎性蛋白3 α,并且它们化学吸引骨髓来源的未成熟但不成熟的DC。使用各种趋化因子或防御素与非免疫原性肿瘤抗原融合,我们研究了它们将抗原递送至免疫细胞亚群以引发抗肿瘤免疫的能力。我们证明,DNA免疫与β-防御素2或炎性趋化因子的融合结构,靶向未成熟的DC,但不是稳态趋化因子次级淋巴组织趋化因子,CCL 21,或基质细胞衍生因子1,CXCL 12,化学吸引成熟的DC,引发不道德的,保护性和治疗性免疫对两种不同的同源淋巴瘤。
Chemokine receptors are differentially expressed on immature and mature dendritic cells (DQ. Herein, we demonstrate for the first time that murine antimicrobial peptides beta -defensins 2 and 3 bind murine CCR6, similarly to inflammatory chemokine macrophage-inflammatory protein 3 alpha, and they chemoattract bone marrow-derived immature, but not mature DC. Using various chemokines or defensins fused with nonimmunogenic tumor Ags, we studied their capacity to delivery Ags to subsets of immune cells to elicit antitumor immunity. We demonstrate that DNA immunizations with fusion constructs with beta -defensin 2 or inflammatory chemokines that target immature DC, but not homeostatic chemokines secondary lymphoid tissue chemokine, CCL21, or stromal cell-derived factor 1, CXCL12, which chemoattract mature DC, elicit Immoral, protective, and therapeutic immunity against two different syngeneic lymphomas.