杜克大学医学院免疫学系,NIH呼吸生物学研究实验室等处的研究人员在Nature Immunology上发表免疫学的新成果。
当机体面对外界入侵的有害细菌和病毒时,免疫应答是机体应对入侵的关键第一步。杜克大学新的研究成果将为疫苗设计和自体免疫疾病的研究带来新的启示。领导这一研究的是杜克大学医学院的免疫学和心脏学专家Michael Gunn。
经典的免疫学理论认为,1型辅助T细胞应答是病毒免疫和细菌免疫的关键所在,免疫学家相信,TH1(1型辅助T细胞)应答能被少数的免疫细胞激活,这种少数的细胞被称为树突细胞。当免疫系统被感染或是疫苗激活时,树突细胞从周围组织迁徙到淋巴结激活T细胞产生应答。
但是杜克大学的研究者发现,激活T细胞不是来自周围组织的树突细胞,而是来自血液中的单核细胞,在感染发生后其从血液中直接赶去感染部位激活TH1引发免疫应答。这一结果改写了经典的免疫学理论,这也解释了为何我们研发树突细胞疫苗总失败。
Michael发现,感染发生后血液中的炎症单核细胞会转变为CD11C+11bhiGr-1+炎性树突细胞,并集结移动进入淋巴结,激活TH1细胞。在这一过程中需要趋化因子受体CCR2参与。
这一研究结果表明血液中炎性单核细胞衍生的树突细胞在TH1免疫应答过程中起关键的激活作用,Michael下一步将研究不同条件下血液衍生的树突细胞对免疫系统的激活情况,这些成果也许对自体免疫疾病和疫苗研究有更佳的指导作用。
该研究成果受到NIH的资助。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Immunology 1 March 2009 | doi:10.1038/ni.1707
Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses
Hideki Nakano1,2,3,6, Kaifeng Lisa Lin2,6, Manabu Yanagita1,5, Chantal Charbonneau1, Donald N Cook3, Terutaka Kakiuchi4 & Michael D Gunn1,2
Abstract
T helper type 1 (TH1)-polarized immune responses, which confer protection against intracellular pathogens, are thought to be initiated by dendritic cells (DCs) that enter lymph nodes from peripheral tissues. Here we found after viral infection or immunization, inflammatory monocytes were recruited into lymph nodes directly from the blood to become CD11c+CD11bhiGr-1+ inflammatory DCs, which produced abundant interleukin 12p70 and potently stimulated TH1 responses. This monocyte extravasation required the chemokine receptor CCR2 but not the chemokine CCL2 or receptor CCR7. Thus, the accumulation of inflammatory DCs and TH1 responses were much lower in Ccr2-/- mice, were preserved in Ccl2-/- mice and were relatively higher in CCL19–CCL21-Ser–deficient plt mutant mice, in which all other lymph node DC types were fewer in number. We conclude that blood-derived inflammatory DCs are important in the development of TH1 immune responses.
1 Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
2 Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
3 Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
4 Department of Immunology, Toho University School of Medicine, Tokyo, Japan.