Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment.
Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment.
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DOI：
10.1084/jem.20100570
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发表时间：
2010-09-27
期刊：
影响因子：
--
通讯作者：
Raulet DH
中科院分区：
文献类型：
--
作者：
Joncker NT;Shifrin N;Delebecque F;Raulet DH
一些成熟的自然杀伤（NK）细胞不能被主要组织相容性复合体（MHC）I分子抑制，这是因为它们缺乏相应的抑制性受体，或者因为宿主缺乏相应的受体的MHC I配体。然而，这种NK细胞仍然保持自身耐受性，并通过激活受体对刺激表现出普遍的低反应性。为了解决NK细胞反应性是否仅在NK细胞分化过程中设定，我们将成熟NK细胞从野生型（WT）转移到MHC I缺陷型宿主，反之亦然。值得注意的是，来自WT小鼠的成熟应答性NK细胞在转移至MHC I缺陷型小鼠后变得低应答，而来自MHC I缺陷型小鼠的成熟低应答性NK细胞在转移至WT小鼠后变得应答。在受体动物中未分裂的成熟NK细胞中，反应性明显改变，表明细胞在转移前已经成熟，活性改变不需要细胞分裂。此外，NK细胞表达KLRG 1，CD 11b，CD 27和Ly 49受体特异性H-2b的百分比转移后没有显着改变。因此，当细胞暴露于改变的MHC环境时，成熟NK细胞的功能活性可以重置。这些发现对于NK细胞功能如何在疾病背景下被削弱或增强具有重要意义。
Some mature natural killer (NK) cells cannot be inhibited by major histocompatibility complex (MHC) I molecules, either because they lack corresponding inhibitory receptors or because the host lacks the corresponding MHC I ligands for the receptors. Such NK cells nevertheless remain self-tolerant and exhibit a generalized hyporesponsiveness to stimulation through activating receptors. To address whether NK cell responsiveness is set only during the NK cell differentiation process, we transferred mature NK cells from wild-type (WT) to MHC I–deficient hosts or vice versa. Remarkably, mature responsive NK cells from WT mice became hyporesponsive after transfer to MHC I–deficient mice, whereas mature hyporesponsive NK cells from MHC I–deficient mice became responsive after transfer to WT mice. Altered responsiveness was evident among mature NK cells that had not divided in the recipient animals, indicating that the cells were mature before transfer and that alterations in activity did not require cell division. Furthermore, the percentages of NK cells expressing KLRG1, CD11b, CD27, and Ly49 receptors specific for H-2b were not markedly altered after transfer. Thus, the functional activity of mature NK cells can be reset when the cells are exposed to a changed MHC environment. These findings have important implications for how NK cell functions may be curtailed or enhanced in the context of disease.
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影响因子：
5.4
作者：
KIESSLING, R;KLEIN, E;WIGZELL, H
通讯作者：
WIGZELL, H
DOI：
10.1073/pnas.0901653106
发表时间：
2009-08-04
影响因子：
11.1
作者：
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通讯作者：
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15.3
作者：
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影响因子：
64.8
作者：
BIX, M;LIAO, NS;RAULET, D
通讯作者：
RAULET, D
影响因子：
20.3
作者：
Costello, RT;Sivori, S;Moretta, A
通讯作者：
Moretta, A