Activation receptor-induced tolerance of mature NK cells in vivo requires signaling through the receptor and is reversible.
Activation receptor-induced tolerance of mature NK cells in vivo requires signaling through the receptor and is reversible.
复制标题
DOI：
10.4049/jimmunol.1003046
复制
发表时间：
2011-03-01
期刊：
影响因子：
--
通讯作者：
Tripathy SK
中科院分区：
文献类型：
--
作者：
Bolanos FD;Tripathy SK
自然杀伤（NK）细胞应答由通过激活和抑制细胞表面受体接收的信号决定。Ly 49 H是一种NK细胞特异性活化受体，其解释了对鼠巨细胞病毒（MCMV）的遗传抗性。Ly 49 H受体已被证明与两种衔接蛋白（DAP 12和DAP 10）相互作用。在MCMV感染的情况下，m157（MCMV编码的Ly 49 H配体）与Ly 49 H的相互作用导致表达Ly 49 H的NK细胞活化。然而，Ly 49 H与m157的慢性暴露在这些相同的细胞中诱导耐受性。这种耐受性的机制仍然知之甚少。使用转基因小鼠模型，我们证明，在Ly 49 H + NK细胞的耐受性诱导慢性暴露于m157，在体内，需要通过Ly 49 H接头蛋白DAP 12的信号，但不是DAP 10接头蛋白。此外，来自野生型小鼠的成熟Ly 49 H表达NK细胞在转移到表达m157（m157-Tg）的转基因C57 BL/6小鼠中后24小时可以获得耐受表型。如果将耐受性NK细胞转移到不表达m157蛋白的小鼠中，则耐受性表型可以在体内逆转。因此，连续激活受体接合可以在体内诱导成熟NK细胞的瞬时耐受。这些观察结果为激活受体接合如何塑造NK细胞功能提供了新的见解，并对NK细胞如何响应肿瘤和慢性病毒感染具有重要意义。
Natural killer (NK) cell responses are determined by signals received through activating and inhibitory cell surface receptors. Ly49H is an NK cell-specific activating receptor that accounts for the genetic resistance to murine cytomegalovirus (MCMV). The Ly49H receptor has been shown to interact with two adapter proteins (DAP12 and DAP10). In the context of MCMV infection, interaction of m157 (the MCMV-encoded ligand for Ly49H) with Ly49H results in activation of Ly49H-expressing NK cells. Chronic exposure of Ly49H with m157, however, induces tolerance in these same cells. The mechanism of this tolerance remains poorly understood. Using a transgenic mouse model, we demonstrate that induction of tolerance in Ly49H+ NK cells by chronic exposure to m157, in vivo, requires signaling through the Ly49H adaptor protein DAP12, but not the DAP10 adaptor protein. Furthermore, mature Ly49H-expressing NK cells from wild-type mice can acquire a tolerant phenotype by twenty-four hours post transfer into a transgenic C57BL/6 mouse that expresses m157 (m157-Tg). The tolerant phenotype can be reversed, in vivo, if tolerant NK cells are transferred to mice that do not express the m157 protein. Thus, continuous activating receptor engagement can induce a transient tolerance in mature NK cells in vivo. These observations provide new insight into how activating receptor engagement shapes NK cell function and has important implications in how NK cells respond to tumors and during chronic viral infection.
登录
查看更多内容
影响因子：
4.4
作者：
Davis, Aja H.;Guseva, Natalya V.;Heusel, Jonathan W.
通讯作者：
Heusel, Jonathan W.
影响因子：
4.4
作者：
Mason, Llewellyn H.;Willette-Brown, Jami;McVicar, Daniel W.
通讯作者：
McVicar, Daniel W.
影响因子：
56.9
作者：
Brown, MG;Dokun, AO;Yokoyama, WM
通讯作者：
Yokoyama, WM
DOI：
10.1084/jem.20100570
发表时间：
2010-09-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Joncker NT;Shifrin N;Delebecque F;Raulet DH
通讯作者：
Raulet DH
影响因子：
20.3
作者：
Arnon, TI;Achdout, H;Mandelboim, O
通讯作者：
Mandelboim, O