2012年8月31日 訊 /生物谷BIOON/ --葉史瓦大學(xué)阿爾伯特·愛(ài)因斯坦醫(yī)學(xué)院的研究人員發(fā)現(xiàn)免疫系統(tǒng)一種新的機(jī)制來(lái)應(yīng)對(duì)感染。該研究開(kāi)拓了目前對(duì)免疫力的理解,并可能導(dǎo)致開(kāi)發(fā)出促進(jìn)疫苗抗感染有效性的新策略。相關(guān)研究結(jié)果發(fā)表在8月30日的Immunity雜志上,。
Grégoire Lauvau,Ph.D表示免疫系統(tǒng)借助記憶性CD8+T細(xì)胞保護(hù)機(jī)體免受細(xì)菌和病毒等微生物的感染。如果有人感染微生物,,記憶性CD8+T細(xì)胞會(huì)識(shí)別入侵者,,并迅速形成能追捕和摧毀微生物和病毒的具有細(xì)胞毒性的T細(xì)胞集群。這種高度的特異性免疫應(yīng)答形成是大多數(shù)疫苗作用的基礎(chǔ),,但疫苗使得免疫系統(tǒng)感染作出反應(yīng)可能需要數(shù)周之久,。
這項(xiàng)新研究表明,免疫系統(tǒng)有另外一個(gè)更快的方法來(lái)應(yīng)對(duì)感染,,了解這一機(jī)制可用來(lái)開(kāi)發(fā)能快速起效的疫苗,。研究負(fù)責(zé)人、微生物學(xué)和免疫學(xué)副教授Grégoire Lauvau博士說(shuō):我們的研究表明,,其實(shí)早在記憶CD8+T細(xì)胞在遇到抗原之前,,針對(duì)病原體的特異性記憶CD8+T細(xì)胞就被激活了。
Lauvau博士和他的同事發(fā)現(xiàn),,這種快速的免疫反應(yīng)是由一種稱(chēng)為炎癥性單核細(xì)胞的白細(xì)胞產(chǎn)生的,,免疫系統(tǒng)檢測(cè)到感染后,招募單核細(xì)胞向受感染組織聚集,,在那里免疫細(xì)胞因子釋放炎癥信號(hào),,這些炎癥信號(hào)激活記憶性CD8+T細(xì)胞,殺滅病原體,但同時(shí)也激活人體內(nèi)自然殺手細(xì)胞(Natural Killer Cells),。其結(jié)果是產(chǎn)生一個(gè)保護(hù)性的免疫環(huán)境,,能夠抵御任何形式的微生物包括病毒、細(xì)菌或寄生蟲(chóng),。但只有當(dāng)記憶性CD8+T細(xì)胞接受到微生物抗原信號(hào)后,,免疫系統(tǒng)才會(huì)針對(duì)微生物進(jìn)行攻擊。
Lauvau博士說(shuō):我們不是說(shuō)識(shí)抗原對(duì)免疫反應(yīng)是不重要的,,你只是在免疫反應(yīng)的后續(xù)階段需要抗原以便引起記憶性CD8 + T細(xì)胞的增殖,,以此得到充分的病原體特異性保護(hù)。論文主要作者為Saïdi M'Homa Soudja博士,、Anne Ruiz,、Julien Marie博士等人。這項(xiàng)研究主要是國(guó)家過(guò)敏和傳染病研究所(AI095835),、美國(guó)國(guó)立衛(wèi)生研究院和愛(ài)因斯坦資金資助,。(生物谷:Bioon.com)
doi:10.1016/j.immuni.2012.05.029
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Inflammatory Monocytes Activate Memory CD8 T and Innate NK Lymphocytes Independent of Cognate Antigen during Microbial Pathogen Invasion
Sadi M'Homa Soudja, Anne L. Ruiz, Julien C. Marie, Grégoire Lauvau.
Memory CD8+ T cells induced upon immunization exhibit improved functional features that contribute to protection of immunized hosts. Although both cognate antigen recognition and inflammation are important for memory CD8+ T cell reactivation, the relative contribution of these factors and the cell types providing these signals in vivo are poorly defined. Here, we show that Ly6C+CCR2+ inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8+ T and NK lymphocytes activation by differentiating into interleukin-18 (IL-18)- and IL-15-producing cells in an inflammasome and type I interferon-IRF3-dependent manner. Memory CD8+ T cells became potent effector cells by sensing inflammation from monocytes independently of their cognate antigen. Like NK cells, they underwent rapid mobilization, upregulated intense and sustained effector functions during bacterial, viral, and parasitic infections, and contributed to innate responses and protection in vivo. Thus, inflammatory monocyte-derived IL-18 and IL-15 are critical to initiate memory CD8+ T and NK lymphocytes differentiation into antimicrobial effector cells.