在中國科學(xué)院、科技部和國家自然科學(xué)基金委的支持下,，中科院生物物理所感染免疫中心的研究人員在T細(xì)胞抑制天然免疫細(xì)胞炎癥反應(yīng)方面取得突破性進(jìn)展,，研究成果在線發(fā)表于9月23日的《自然·醫(yī)學(xué)》,。
天然免疫系統(tǒng)是人體抵御病毒入侵的第一道防線，在病毒感染的數(shù)小時(shí)內(nèi),，天然免疫系統(tǒng)首先識別病毒并產(chǎn)生抗病毒的干擾素,，同時(shí)產(chǎn)生炎癥反應(yīng)。經(jīng)典的免疫調(diào)控理論證明,，這種天然免疫反應(yīng)對于數(shù)天后產(chǎn)生的T細(xì)胞免疫并清除病毒感染起著至關(guān)重要的調(diào)控作用,。生物物理所唐宏研究組和海外團(tuán)隊(duì)付陽心研究組通過多年的研究, 發(fā)現(xiàn)在肝炎病毒感染的極早期(<2天),，未被激活的T細(xì)胞對于控制天然免疫細(xì)胞產(chǎn)生的炎癥反應(yīng)期至關(guān)重要的抑制作用。病毒感染適應(yīng)性免疫系統(tǒng)缺陷的裸鼠或剔除T細(xì)胞的小鼠后,，小鼠因天然免疫系統(tǒng)被激活導(dǎo)致的炎癥因子飆升而劇烈死亡,；過繼性輸入T細(xì)胞或者進(jìn)一步剔除自然殺傷細(xì)胞(NK)后小鼠重新存活，炎癥反應(yīng)也得到了有效抑制,。這一發(fā)現(xiàn)加深了人們對于炎癥反應(yīng)的認(rèn)識,，并提出了T細(xì)胞參與天然免疫反應(yīng)的負(fù)性調(diào)控的新理論。這一發(fā)現(xiàn)同時(shí)對于臨床上深入了解病毒性感染的炎癥反應(yīng)和病毒清除機(jī)理,，免疫低下病人(新生兒，老年人,，器官移植患者或艾滋病人)機(jī)會(huì)性感染的控制具有極高的理論價(jià)值,。
生物物理所感染免疫中心由9名百人計(jì)劃研究員以及7名“海外知名學(xué)者”免疫團(tuán)隊(duì)組成，共同就病毒性肝炎等重大傳染性疾病開展廣泛深入的合作研究,。這種合作模式在過去的兩年中,，已在慢性乙肝和丙肝的免疫應(yīng)答機(jī)制以及免疫干預(yù)手段方面取得多項(xiàng)實(shí)質(zhì)性進(jìn)展，同時(shí)在免疫遺傳學(xué)和結(jié)構(gòu)免疫學(xué)等交叉研究領(lǐng)域也取得了喜人的成果,。這種合作模式的進(jìn)一步發(fā)展無疑將對我院免疫學(xué)和循征醫(yī)學(xué)(translational medicine)研究起積極推動(dòng)作用,。(生物物理研究所)
原始出處:
Nature Medicine
Published online: 23 September 2007 | doi:10.1038/nm1633
Adaptive immune cells temper initial innate responses
Kwang Dong Kim1,2,3, Jie Zhao1,3, Sogyong Auh2, Xuanming Yang1, Peishuang Du1, Hong Tang1 & Yang-Xin Fu1,2
Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells1, 2, 3, 4. Lymphocyte-deficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1–deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25-Foxp3- or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.
Center for Infection and Immunity and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Da Tun Road, Chaoyang District, Beijing 100101, China.
Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA,
These authors contributed equally to this work.
Correspondence to: Hong Tang1 e-mail: [email protected]
Correspondence to: Yang-Xin Fu1,2 e-mail: [email protected]
