在中国科学院、科技部和国家自然科学基金委的支持下，中科院生物物理所感染免疫中心的研究人员在T细胞抑制天然免疫细胞炎症反应方面取得突破性进展，研究成果在线发表于9月23日的《自然·医学》。
天然免疫系统是人体抵御病毒入侵的第一道防线，在病毒感染的数小时内，天然免疫系统首先识别病毒并产生抗病毒的干扰素，同时产生炎症反应。经典的免疫调控理论证明，这种天然免疫反应对于数天后产生的T细胞免疫并清除病毒感染起着至关重要的调控作用。生物物理所唐宏研究组和海外团队付阳心研究组通过多年的研究, 发现在肝炎病毒感染的极早期(<2天)，未被激活的T细胞对于控制天然免疫细胞产生的炎症反应期至关重要的抑制作用。病毒感染适应性免疫系统缺陷的裸鼠或剔除T细胞的小鼠后，小鼠因天然免疫系统被激活导致的炎症因子飙升而剧烈死亡；过继性输入T细胞或者进一步剔除自然杀伤细胞(NK)后小鼠重新存活，炎症反应也得到了有效抑制。这一发现加深了人们对于炎症反应的认识，并提出了T细胞参与天然免疫反应的负性调控的新理论。这一发现同时对于临床上深入了解病毒性感染的炎症反应和病毒清除机理，免疫低下病人(新生儿，老年人，器官移植患者或艾滋病人)机会性感染的控制具有极高的理论价值。
生物物理所感染免疫中心由9名百人计划研究员以及7名“海外知名学者”免疫团队组成，共同就病毒性肝炎等重大传染性疾病开展广泛深入的合作研究。这种合作模式在过去的两年中，已在慢性乙肝和丙肝的免疫应答机制以及免疫干预手段方面取得多项实质性进展，同时在免疫遗传学和结构免疫学等交叉研究领域也取得了喜人的成果。这种合作模式的进一步发展无疑将对我院免疫学和循征医学(translational medicine)研究起积极推动作用。(生物物理研究所)
原始出处:
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: tanghong@moon.ibp.ac.cn
Correspondence to: Yang-Xin Fu1,2 e-mail: yfu@uchicago.edu
