杜克大學醫(yī)學院免疫學系,，NIH呼吸生物學研究實驗室等處的研究人員在Nature Immunology上發(fā)表免疫學的新成果,。
當機體面對外界入侵的有害細菌和病毒時，免疫應答是機體應對入侵的關鍵第一步,。杜克大學新的研究成果將為疫苗設計和自體免疫疾病的研究帶來新的啟示,。領導這一研究的是杜克大學醫(yī)學院的免疫學和心臟學專家Michael Gunn。
經典的免疫學理論認為,，1型輔助T細胞應答是病毒免疫和細菌免疫的關鍵所在,，免疫學家相信，TH1（1型輔助T細胞）應答能被少數的免疫細胞激活,，這種少數的細胞被稱為樹突細胞,。當免疫系統(tǒng)被感染或是疫苗激活時，樹突細胞從周圍組織遷徙到淋巴結激活T細胞產生應答,。
但是杜克大學的研究者發(fā)現(xiàn),，激活T細胞不是來自周圍組織的樹突細胞，而是來自血液中的單核細胞,，在感染發(fā)生后其從血液中直接趕去感染部位激活TH1引發(fā)免疫應答,。這一結果改寫了經典的免疫學理論，這也解釋了為何我們研發(fā)樹突細胞疫苗總失敗,。
Michael發(fā)現(xiàn),，感染發(fā)生后血液中的炎癥單核細胞會轉變?yōu)镃D11C+11bhiGr-1+炎性樹突細胞，并集結移動進入淋巴結,，激活TH1細胞,。在這一過程中需要趨化因子受體CCR2參與。
這一研究結果表明血液中炎性單核細胞衍生的樹突細胞在TH1免疫應答過程中起關鍵的激活作用,，Michael下一步將研究不同條件下血液衍生的樹突細胞對免疫系統(tǒng)的激活情況,，這些成果也許對自體免疫疾病和疫苗研究有更佳的指導作用。
該研究成果受到NIH的資助,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
