杜克大學(xué)醫(yī)學(xué)院免疫學(xué)系,，NIH呼吸生物學(xué)研究實(shí)驗(yàn)室等處的研究人員在Nature Immunology上發(fā)表免疫學(xué)的新成果。
當(dāng)機(jī)體面對(duì)外界入侵的有害細(xì)菌和病毒時(shí),，免疫應(yīng)答是機(jī)體應(yīng)對(duì)入侵的關(guān)鍵第一步,。杜克大學(xué)新的研究成果將為疫苗設(shè)計(jì)和自體免疫疾病的研究帶來新的啟示。領(lǐng)導(dǎo)這一研究的是杜克大學(xué)醫(yī)學(xué)院的免疫學(xué)和心臟學(xué)專家Michael Gunn,。
經(jīng)典的免疫學(xué)理論認(rèn)為,，1型輔助T細(xì)胞應(yīng)答是病毒免疫和細(xì)菌免疫的關(guān)鍵所在，免疫學(xué)家相信,，TH1（1型輔助T細(xì)胞）應(yīng)答能被少數(shù)的免疫細(xì)胞激活,，這種少數(shù)的細(xì)胞被稱為樹突細(xì)胞。當(dāng)免疫系統(tǒng)被感染或是疫苗激活時(shí)，樹突細(xì)胞從周圍組織遷徙到淋巴結(jié)激活T細(xì)胞產(chǎn)生應(yīng)答,。
但是杜克大學(xué)的研究者發(fā)現(xiàn),，激活T細(xì)胞不是來自周圍組織的樹突細(xì)胞，而是來自血液中的單核細(xì)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(yīng)答,。這一結(jié)果改寫了經(jīng)典的免疫學(xué)理論，這也解釋了為何我們研發(fā)樹突細(xì)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(xì)胞會(huì)轉(zhuǎn)變?yōu)镃D11C+11bhiGr-1+炎性樹突細(xì)胞，并集結(jié)移動(dòng)進(jìn)入淋巴結(jié),，激活TH1細(xì)胞,。在這一過程中需要趨化因子受體CCR2參與。
這一研究結(jié)果表明血液中炎性單核細(xì)胞衍生的樹突細(xì)胞在TH1免疫應(yīng)答過程中起關(guān)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(xì)胞對(duì)免疫系統(tǒng)的激活情況,，這些成果也許對(duì)自體免疫疾病和疫苗研究有更佳的指導(dǎo)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.
