NK cell-mediated lysis of autologous HCMV-infected skin fibroblasts is highly variable among NK cell clones and polyclonal NK cell lines

NK cell-mediated lysis of autologous HCMV-infected skin fibroblasts is highly variable among NK cell clones and polyclonal NK cell lines
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DOI:
10.1006/clim.2002.5273
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发表时间:
2002-11-01
影响因子:
8.6
通讯作者:
Parham, P
Parham, P
中科院分区:
医学3区
文献类型:
--
作者:
Carr, WH;Little, AM;Parham, P

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在体外检测了自体自然杀伤(NK)细胞对人巨细胞病毒(HCMV)感染的成纤维细胞的溶解作用。对于NK细胞克隆,在mRNA和细胞表面蛋白水平测定受体表达,并与HCMV AD 169株感染的成纤维细胞的裂解进行比较,其中HILA I类下调>70%。这些克隆裂解AD 169感染的成纤维细胞的能力范围很广,既不与抑制性KIR、白细胞抑制性受体-1或CD 94:NKG 2A受体的表达相关,也不与每个克隆表达的不同抑制性KIR的数量相关。一些多克隆NK细胞系优先裂解AD 169感染的细胞,并类似地裂解突变病毒RV 798感染的成纤维细胞,其缺乏下调HLA I类的基因。这些结果表明,HCMV感染的自体成纤维细胞的NK细胞裂解比涉及HLA I类下调和未能参与抑制性自身特异性KIR的简单的自身缺失机制更复杂。(C)2002 Elsevier Science(美国)。
Lysis of human cytomegalovirus (HCMV)-infected fibroblasts by autologous natural killer (NK) cells was examined in vitro. For NK cell clones, receptor expression was determined at the level of mRNA and cell-surface protein and compared to the lysis of HCMV AD169 strain-infected fibroblasts in which HILA class I was >70% downregulated. The clones ranged broadly in their ability to lyse AD169-infected fibroblasts, correlating neither with the expression of inhibitory KIR, leukocyte inhibitory receptor-1, or CD94:NKG2A receptors nor with the number of different inhibitory KIR expressed per clone. Some lines of polyclonal NK cells preferentially lysed AD169-infected cells and similarly lysed fibroblasts infected with mutant virus RV798, which lacks the genes for downregulating HLA class I. These results demonstrate that NK cell lysis of HCMV-infected autologous fibroblasts is more complex than a simple missing-self mechanism involving downregulation of HLA class I and failure to engage inhibitory self-specific KIR. (C) 2002 Elsevier Science (USA).