在中國科學院,、科技部和國家自然科學基金委的支持下,，中科院生物物理所感染免疫中心的研究人員在T細胞抑制天然免疫細胞炎癥反應方面取得突破性進展，研究成果在線發(fā)表于9月23日的《自然·醫(yī)學》,。
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，同時產(chǎn)生炎癥反應,。經(jīng)典的免疫調(diào)控理論證明,，這種天然免疫反應對于數(shù)天后產(chǎn)生的T細胞免疫并清除病毒感染起著至關重要的調(diào)控作用。生物物理所唐宏研究組和海外團隊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細胞對于控制天然免疫細胞產(chǎn)生的炎癥反應期至關重要的抑制作用。病毒感染適應性免疫系統(tǒng)缺陷的裸鼠或剔除T細胞的小鼠后,，小鼠因天然免疫系統(tǒng)被激活導致的炎癥因子飆升而劇烈死亡,；過繼性輸入T細胞或者進一步剔除自然殺傷細胞(NK)后小鼠重新存活，炎癥反應也得到了有效抑制,。這一發(fā)現(xiàn)加深了人們對于炎癥反應的認識,，并提出了T細胞參與天然免疫反應的負性調(diào)控的新理論。這一發(fā)現(xiàn)同時對于臨床上深入了解病毒性感染的炎癥反應和病毒清除機理,，免疫低下病人(新生兒,，老年人，器官移植患者或艾滋病人)機會性感染的控制具有極高的理論價值,。
生物物理所感染免疫中心由9名百人計劃研究員以及7名“海外知名學者”免疫團隊組成,，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答機制以及免疫干預手段方面取得多項實質(zhì)性進展,，同時在免疫遺傳學和結構免疫學等交叉研究領域也取得了喜人的成果。這種合作模式的進一步發(fā)展無疑將對我院免疫學和循征醫(yī)學(translational medicine)研究起積極推動作用,。(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]
