Trogocytosis-based generation of suppressive NK cells
Trogocytosis-based generation of suppressive NK cells
复制标题
DOI：
10.1038/sj.emboj.7601570
复制
发表时间：
2007-03-07
期刊：
影响因子：
11.4
通讯作者：
LeMaoult, Joel
中科院分区：
文献类型：
--
作者：
Caumartin, Julien;Favier, Benoit;LeMaoult, Joel
巨噬细胞增多症是指一个细胞的细胞膜和相关分子被另一个细胞快速摄取。自然杀伤(NK)细胞和肿瘤之间的滋养细胞作用已经被描述，但NK-肿瘤靶标物质交换的功能相关性尚不清楚。我们研究了免疫抑制分子HLA-G是否可以从肿瘤细胞转移到NK细胞，以及这种转移是否具有功能性后果。我们发现，被激活的NK细胞从肿瘤细胞中获得了人类白细胞抗原-G1，并且在这种获得之后，NK细胞停止了增殖，不再具有细胞毒性，并且表现为抑制性细胞。这类细胞可以抑制其他NK细胞的细胞毒功能，保护NK敏感的肿瘤细胞不被细胞溶解。这些数据首次证明，人类白细胞抗原-G1的巨噬细胞增多可能是免疫逃避的主要机制，它通过效应细胞发挥作用，使其局部、暂时但有效地发挥抑制细胞的作用。讨论了免疫和非免疫细胞共用膜对效应器功能和免疫反应结果的更广泛的影响。
Trogocytosis is a fast uptake of membranes and associated molecules from one cell by another. Trogocytosis between natural killer (NK) cells and tumors is already described, but the functional relevance of NK-tumor targets material exchange is unclear. We investigated whether the immunosuppressive molecule HLA-G that is commonly expressed by tumors in vivo and known to block NK cytolytic function, could be transferred from tumor cells to NK cells, and if this transfer had functional consequences. We show that activated NK cells acquire HLA-G1 from tumor cells, and that upon this acquisition, NK cells stop proliferating, are no longer cytotoxic, and behave as suppressor cells. Such cells can inhibit other NK cells' cytotoxic function and protect NK-sensitive tumor cells from cytolysis. These data are the first demonstration that trogocytosis of HLA-G1 can be a major mechanism of immune escape that acts through effector cells made to act as suppressor cells locally, temporarily, but efficiently. The broader consequences of membrane sharing between immune and non-immune cells on the function of effectors and the outcome of immune responses are discussed.