The lytic potential of human liver NK cells is restricted by their limited expression of inhibitory killer Ig-like receptors.
The lytic potential of human liver NK cells is restricted by their limited expression of inhibitory killer Ig-like receptors.
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DOI：
10.4049/jimmunol.0900541
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发表时间：
2009-08-01
期刊：
影响因子：
--
通讯作者：
DeMatteo RP
中科院分区：
文献类型：
--
作者：
Burt BM;Plitas G;Zhao Z;Bamboat ZM;Nguyen HM;Dupont B;DeMatteo RP
人类肝脏富含天然杀伤细胞（NK细胞），这是先天免疫系统的有效效应器。我们已经确定，从肝脏恶性肿瘤患者的手术标本中新鲜分离的肝脏NK细胞比自体血液NK细胞具有更低的细胞溶解活性。这种差异是由于肝脏中CD 16 − NK细胞的比例较高，并且与血液对应物相比，CD 16+肝脏NK细胞的细胞毒性降低。与CD 16+血NK细胞相比，CD 16+肝NK细胞具有相似的活化NK受体表达，并且具有相似的细胞内颗粒酶B和穿孔素含量。CD 16+肝脏NK细胞中具有自身MHC I类特异性抑制性杀伤免疫球蛋白样受体（自身KIR）的细胞比例减少，而自身KIR NKG 2Apos和自身KIR NKG 2Aneg细胞比例增加。使用细胞内干扰素-γ（IFN-γ）产生的单细胞分析和细胞毒性试验，我们确定表达自身KIR的CD 16+肝脏NK细胞比不表达自身KIR分子的细胞对靶细胞的反应更强。当用IL-2刺激或与LPS或PolyI：C活化的自体肝Kupffer细胞一起培养时，CD 16+肝NK细胞获得细胞溶解功能。因此，人肝脏含有NK细胞亚群，其具有降低的效应子功能，但在适当的炎症条件下成为强效杀手。
The human liver is enriched in natural killer cells (NK cells) which are potent effectors of the innate immune system. We have determined that liver NK cells freshly isolated from surgical specimens from patients with hepatic malignancy have less cytolytic activity than autologous blood NK cells. This difference was due to a higher proportion of CD16− NK cells in the liver and reduced cytotoxicity by CD16+ liver NK cells compared with their blood counterparts. CD16+ liver NK cells had similar expression of activating NK receptors and had similar intracellular granzyme B and perforin content compared with CD16+ blood NK cells. CD16+ liver NK cells contained a reduced fraction of cells with inhibitory killer immunoglobulin-like receptors specific for self-MHC class I (self-KIR) and an increased fraction of self-KIRnegNKG2Apos and self-KIRnegNKG2Aneg cells. Using single-cell analysis of intracellular interferon-gamma (IFN-γ) production and cytotoxicity assays, we determined that CD16+ liver NK cells expressing self-KIR were more responsive to target cells than those cells that did not express self-KIR molecules. CD16+ liver NK cells gained cytolytic function when stimulated with IL-2 or cultured with LPS or PolyI:C-activated autologous liver Kupffer cells. Thus, the human liver contains NK cell subsets which have reduced effector function, but under appropriate inflammatory conditions become potent killers.
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DOI：
10.1084/jem.20010938
发表时间：
2002-02-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gerosa F;Baldani-Guerra B;Nisii C;Marchesini V;Carra G;Trinchieri G
通讯作者：
Trinchieri G
影响因子：
25.7
作者：
KNOLLE, P;SCHLAAK, J;GERKEN, G
通讯作者：
GERKEN, G
DOI：
10.4049/jimmunol.0803404
发表时间：
2009-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bamboat ZM;Stableford JA;Plitas G;Burt BM;Nguyen HM;Welles AP;Gonen M;Young JW;DeMatteo RP
通讯作者：
DeMatteo RP
DOI：
10.1084/jem.20061287
发表时间：
2007-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dunn C;Brunetto M;Reynolds G;Christophides T;Kennedy PT;Lampertico P;Das A;Lopes AR;Borrow P;Williams K;Humphreys E;Afford S;Adams DH;Bertoletti A;Maini MK
通讯作者：
Maini MK
影响因子：
6.2
作者：
DAAR, AS;FUGGLE, SV;MORRIS, PJ
通讯作者：
MORRIS, PJ