HLA-G expression protects porcine endothelial cells against natural killer cell-mediated xenogeneic cytotoxicity.
HLA-G expression protects porcine endothelial cells against natural killer cell-mediated xenogeneic cytotoxicity.
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HLA-G 表达可保护猪内皮细胞免受自然杀伤细胞介导的异种细胞毒性。
DOI：
10.1097/00007890-199901150-00005
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发表时间：
1999
期刊：
影响因子：
6.2
通讯作者：
Mohanakumar,T
中科院分区：
文献类型：
--
作者：
Sasaki,H;Xu,XC;Smith,DM;Howard,T;Mohanakumar,T
背景：自然杀伤(NK)细胞是异种移植中细胞反应的主要组成部分。NK细胞活化和NK细胞介导的细胞毒作用直接阻碍了异种器官在人类移植中的潜在应用。方法：通过脂质体转染法将人全长的人类白细胞抗原G基因组DNA导入猪主动脉内皮细胞，以确定人类白细胞抗原G是否能保护异种细胞免受人类NK细胞的杀伤。用抗HLAI类骨架抗体PA2进行免疫荧光染色，证实了HLAG在PAECs表面的表达。6.以人新鲜外周血淋巴细胞为NK效应细胞，以人类白细胞抗原G基因修饰的PAECs为靶细胞，进行51Cr释放实验。用纯化的抗人HLAI类抗体PA2的F(ab‘)2部分抗体封闭PAECs，证实了HLAG对人多克隆NK细胞的抑制作用。6.结果：当7名健康供者的外周血淋巴细胞携带纯合子的HLA-Cw3或-Cw4作为NK效应细胞时，PAECs上的HLA-G的表达对NK介导的裂解具有显著的保护作用(抑制范围为52-100%)。这种保护作用可被纯化的抗HLAI类抗体F(ab‘)2部分所抑制，提示PAECs的保护作用是通过表达HLAG来实现的。这些结果表明，在没有其他非经典的HLAI类分子的情况下，单独表达HLAG足以抑制人NK细胞的裂解。这些发现提示了利用人类白细胞抗原G来克服NK细胞介导的对猪内皮细胞的细胞毒性的方法，猪内皮细胞被认为是异种细胞排斥反应中产生的第一种细胞类型。
Background.Natural killer (NK) cells are major component of the cellular response in xenotransplantation. NK cell activation and NK cell-mediated cytotoxicity can be a direct barrier to the potential use of xenogeneic organs in human transplantation.Methods.To determine if HLA-G would protect porcine xenogeneic cells from human NK cell lysis, human full-length HLA-G genomic DNA was transfected into porcine aortic endothelial cell (PAECs) by the lipofection method. Surface expression of HLA-G in transfected PAECs was confirmed by immunofluorescence staining with anti-HLA class I framework antibody, PA2. 6. Fresh human peripheral blood lymphocytes were used as NK effector cells with HLA-G-transfected PAECs as targets in a 51 Cr release assay. The inhibition of human polyclonal NK cells by HLA-G expression on PAECs was confirmed by antibody blocking using purified F (ab′) 2 portion of anti-human HLA class I antibody PA2. 6.Results.Expression of HLA-G on PAECs conferred a significant protection against NK-mediated lysis (range: 52-100% inhibition) when peripheral blood lymphocytes from seven healthy donors, bearing either homozygous HLA-Cw3 or-Cw4 used as NK effector cells. Such protection was inhibited by purified F (ab′) 2 portion of anti-HLA class I antibody, indicating that the protection of PAECs was directly mediated by HLA-G expression.Conclusions.Expression of HLA-G on PAECs protected xenogeneic PAECs against human polyclonal NK cell-mediated lysis. These results indicate that the expression of HLA-G alone in the absence of other nonclassical HLA class I molecules is sufficient to inhibit human NK cell lysis. These findings suggest methods utilizing HLA-G to overcome NK cell-mediated cytotoxicity against porcine endothelial cells, considered the first cell type effected during xenograft cellular rejection.
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影响因子：
9.2
作者：
Diehl, M;Munz, C;Rammensee, HG
通讯作者：
Rammensee, HG
人类组织相容性白细胞抗原 (HLA)-G 分子抑制 NKAT3 表达的自然杀伤细胞
影响因子：
15.3
作者：
C. Münz;N. Holmes;A. King;Y. W. Loke;M. Colonna;H. Schild;H. Rammensee
通讯作者：
H. Rammensee
NKB1 和 HP-3E4 NK 细胞受体是结构不同的糖蛋白，独立识别多态性 HLA-B 和 HLA-C 分子。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lanier,LL;Gumperz,JE;Parham,P;Melero,I;Lopez-Botet,M;Phillips,JH
通讯作者：
Phillips,JH
DOI：
10.1073/pnas.95.9.5199
发表时间：
1998-04-28
影响因子：
11.1
作者：
Lee, N;Llano, M;Geraghty, DE
通讯作者：
Geraghty, DE
人类自然杀伤细胞诱导猪内皮细胞单层的形态变化。
影响因子：
6.2
作者：
Malyguine,AM;Saadi,S;Platt,JL;Dawson,JR
通讯作者：
Dawson,JR