美國科學(xué)家近日首次研究發(fā)現(xiàn),，人體免疫系統(tǒng)能夠同時激活和抑制自然殺傷細(xì)胞（NK）的不同免疫響應(yīng),。這一發(fā)現(xiàn)將有助于科學(xué)家更深入地研究器官移植排斥反應(yīng)。相關(guān)論文10月18日在線發(fā)表于《臨床檢查雜志》（The Journal of Clinical Investigation）上。
NK細(xì)胞能夠抵御病毒的入侵,，但是它的有效發(fā)揮作用需要樹突狀細(xì)胞（DCs）的“刺激”,。樹突狀細(xì)胞會附著在NK細(xì)胞的表面，激活相關(guān)受體,，最后這兩種細(xì)胞之間會形成神經(jīng)突觸以進(jìn)行交流,。一般來說，這些突觸是由激活受體或抑制受體組成,，可開啟或關(guān)閉NK細(xì)胞,。
在最新的研究中，美國洛克菲勒大學(xué)的Christian Münz和同事仔細(xì)研究了這種突觸的結(jié)構(gòu),，結(jié)果發(fā)現(xiàn)這兩種受體同時存在,，不過是分別位于突觸不同的區(qū)域。
Münz表示,，這是首次發(fā)現(xiàn)這種交互作用,。這種突觸具有新穎的調(diào)節(jié)機制，兩種受體同時發(fā)揮作用,，調(diào)節(jié)激活和抑制信號,。樹突狀細(xì)胞向NK細(xì)胞釋放不同的信號，抑制了它們殺傷或溶解細(xì)胞的功能,，同時卻激活它們進(jìn)行分化,，釋放出細(xì)胞素信號分子并轉(zhuǎn)變成更強的“殺手”。
Münz表示,，目前的研究只是初級階段。由于樹突狀細(xì)胞與T細(xì)胞之間也存在聯(lián)系,，所以下一步將會深入研究T細(xì)胞激活的生物學(xué)機制,。將來如果能找到一種方法阻止NK細(xì)胞識別樹突狀細(xì)胞，將有可能阻止樹突狀細(xì)胞激活人體免疫系統(tǒng),，使其不會對移植器官產(chǎn)生攻擊反應(yīng),。（科學(xué)網(wǎng) 梅進(jìn)/編譯）
（《臨床檢查雜志》（The Journal of Clinical Investigation），doi:10.1172/JCI31751,，F(xiàn)abienne Brilot,，Christian Münz）
原始出處:
Published October 18, 2007
J. Clin. Invest. doi:10.1172/JCI31751.
NK cell survival mediated through the regulatory synapse with human DCs requires IL-15Rα
Fabienne Brilot, Till Strowig, Susanne M. Roberts, Frida Arrey and Christian Münz
Laboratory of Viral Immunobiology and Christopher H. Browne Center for Immunology and Immune Diseases, Rockefeller University, New York, New York, USA.
Address correspondence to: Christian Münz, Laboratory of Viral Immunobiology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA. Phone: (212) 327-7611; Fax: (212) 327-7887; E-mail: [email protected].
Received for publication February 8, 2007, and accepted in revised form August 15, 2007.
DCs activate NK cells during innate immune responses to viral infections. However, the composition and kinetics of the immunological synapse mediating this interaction are largely unknown. Here, we report the rapid formation of an immunological synapse between human resting NK cells and mature DCs. Although inhibitory NK cell receptors were polarized to this synapse, where they are known to protect mature DCs from NK cell lysis, the NK cell also received activation signals that induced mobilization of intracellular calcium and CD69 upregulation. The high-affinity component of the receptor for IL-15, IL-15Rα, accumulated at the synapse center on NK cells, and blocking of IL-15Rα increased NK cell apoptosis and diminished NK cell survival during their interaction with DCs. Furthermore, IL-15Rα–deficient NK cells, obtained from donors with a history of infectious mononucleosis, showed diminished survival in culture with DCs. Synapse formation was required for IL-15Rα–mediated NK cell survival, because synapse disruption by adhesion molecule blocking decreased DC-induced NK cell survival. These results identify what we believe to be a novel regulatory NK cell synapse with hallmarks of spatially separated inhibitory and activating interactions at its center. We suggest that this synapse formation enables optimal NK cell activation by DCs during innate immune responses.
