前沿：病毒感染打破了自然杀伤细胞对“自身缺失”的耐受性。
Cutting edge: viral infection breaks NK cell tolerance to "missing self".
作者信息
Sun Joseph C, Lanier Lewis L
机构信息
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, CA 94143, USA.
出版信息
J Immunol. 2008 Dec 1;181(11):7453-7. doi: 10.4049/jimmunol.181.11.7453.
Abstract
NK cells attack cells lacking MHC class I, yet MHC class I-deficient mice have normal numbers of NK cells with intact, albeit diminished, functions. Moreover, wild-type NK cells are tolerant of MHC class I-deficient cells in mixed bone marrow chimeras. In this study, we investigated how the absence of MHC class I affects NK cells. NK cells from beta(2)-microglobulin-deficient (B2m(-/-)) and wild-type mice exhibit similar phenotypic and functional characteristics. Both B2m(-/-) and wild-type Ly49H(+) NK cells proliferated robustly and produced IFN-gamma after infection with mouse CMV. NK cells in mixed wild-type:B2m(-/-) chimeric mice were initially tolerant of MHC class I-deficient host cells. However, this tolerance was gradually lost over time and after mouse CMV infection was rapidly broken, with a pronounced rejection of host B2m(-/-) hematopoietic cells. Thus, although NK cells can be held in check against "missing self," acute inflammation driven by infection can rapidly break established self-tolerance.
摘要
自然杀伤（NK）细胞攻击缺乏主要组织相容性复合体（MHC）I类分子的细胞，然而，缺乏MHC I类分子的小鼠却拥有数量正常的NK细胞，其功能虽有所减弱但仍保持完整。此外，在混合骨髓嵌合体中，野生型NK细胞对缺乏MHC I类分子的细胞具有耐受性。在本研究中，我们探究了MHC I类分子的缺失如何影响NK细胞。来自β2-微球蛋白缺陷（B2m-/-）小鼠和野生型小鼠的NK细胞表现出相似的表型和功能特征。在用小鼠巨细胞病毒（CMV）感染后，B2m-/-和野生型Ly49H+ NK细胞均能强劲增殖并产生γ干扰素（IFN-γ）。在野生型:B2m-/-混合嵌合小鼠中的NK细胞最初对缺乏MHC I类分子的宿主细胞具有耐受性。然而，这种耐受性会随着时间逐渐丧失，并且在小鼠CMV感染后会迅速被打破，导致对宿主B2m-/-造血细胞的明显排斥。因此，尽管NK细胞可以因“自身缺失”而受到抑制，但由感染驱动的急性炎症能够迅速打破已建立的自身耐受性。
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