In contrast to anti-tumor activity, YT cell and primary NK cell cytotoxicity for Cryptococcus neoformans bypasses LFA-1
In contrast to anti-tumor activity, YT cell and primary NK cell cytotoxicity for Cryptococcus neoformans bypasses LFA-1
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DOI：
10.1093/intimm/dxp010
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Mody, Christopher H.
中科院分区：
文献类型：
--
作者：
Jones, Gareth J.;Wiseman, Jeremy C. D.;Mody, Christopher H.
NK细胞的细胞毒性需要两个阳性信号来杀死肿瘤。活化受体诱导微管组织中心的极化和脱粒，而白细胞功能相关抗原（LFA）-1是缀合物形成和肌动蛋白聚合所需的，并且在某些情况下可能足以用于NK细胞的细胞毒性。尽管直接杀死真菌的受体尚不清楚，但LFA-1的β 2链CD 18结合机会致病菌新型隐球菌的荚膜和细胞壁的组分，即多糖葡糖醛酸甘露聚糖和半乳糖基甘露聚糖。在此，我们还证明了LFA-1集中在NK细胞表面与C.新人类因此，有令人信服的证据假设NK细胞也会使用LFA-1来识别和杀死C。新人类使用表达或不表达LFA-1的NK细胞系的组合或通过使用CD 18特异性功能性阻断抗体，我们证实NK细胞抗肿瘤活性严重依赖于LFA-1的表达。与肿瘤细胞毒性事件相同，NK细胞与隐球菌靶点形成缀合物，重新排列细胞骨架以形成NK免疫突触并释放含穿孔素的颗粒;然而，这些事件中的每一个都独立于LFA-1发生。此外，NK细胞介导的C.在用CD 18阻断抗体预处理的NK细胞和缺乏细胞表面LFA-1表达的NK细胞中均可检测到新生儿。这些结果表明，在LFA-1表达不存在的情况下，NK细胞完全能够识别靶标（C.新生儿）并保留细胞毒性所需的所有事件。
NK cell cytotoxicity requires two positive signals for killing of tumors. Activation receptors induce polarization of the microtubule organization center and degranulation, while leukocyte function-associated antigen (LFA)-1 is required for conjugate formation and actin polymerization and under some circumstances may be sufficient for NK cell cytotoxicity. Although the receptor for direct killing of fungi is not known, CD18, the beta 2 chain of LFA-1, binds components of the capsule and cell wall of the opportunistic pathogen Cryptococcus neoformans, namely the polysaccharides glucoronoxylomannan and galactoxylomannan. Herein, we also demonstrate that LFA-1 was concentrated in regions of the NK cell surface interacting with C. neoformans. Consequently, there was compelling evidence to hypothesize that NK cells would also use LFA-1 to recognize and kill C. neoformans. Using a combination of NK cell lines that did or did not express LFA-1 or by using a CD18-specific functional blocking antibody, we confirm that NK cell anti-tumor activity is critically dependent upon the expression of LFA-1. Duplicating the events of tumor cytotoxicity, NK cells form conjugates with cryptococcal targets, rearrange the cell cytoskeleton to develop an NK immunologic synapse and release perforin-containing granules; however, each of these events occurred independently of LFA-1. Furthermore, NK cell-mediated killing of C. neoformans was detectable in both NK cells pre-treated with CD18-blocking antibodies and in NK cells lacking cell surface LFA-1 expression. These results demonstrate that in the absence of LFA-1 expression, NK cells are fully capable of recognizing a target (C. neoformans) and retain all of the events required for cytotoxicity.