Natural Killer Cell Receptor Repertoire and Their Ligands, and the Risk of CMV Infection After Kidney Transplantation
Natural Killer Cell Receptor Repertoire and Their Ligands, and the Risk of CMV Infection After Kidney Transplantation
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DOI：
10.1111/j.1600-6143.2008.02431.x
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发表时间：
2008-12-01
影响因子：
8.8
通讯作者：
Villard, J.
中科院分区：
文献类型：
--
作者：
Hadaya, K.;de Rham, C.;Villard, J.
巨细胞病毒（CMV）感染是实体器官移植（SOT）后最常见的病毒性并发症。虽然目前的免疫抑制已知会损害SOT中的抗病毒特异性T细胞免疫，但不受免疫抑制治疗影响的自然杀伤（NK）细胞的潜在作用仍有待确定。为了解决这个问题，我们比较了196例肾移植受者的NK免疫球蛋白样受体（KIR）基因及其HLA同源配体的基因型与CMV感染率。我们已经证明，受体中缺乏抑制性KIR的HLA-C配体和存在激活性KIR基因都与移植后较低的CMV感染率相关。在一组17名急性CMV感染的受者中，通过C型凝集素受体的表达谱和分泌IFN-γ的能力，在诊断后的一段时间内对NK细胞进行表型分析。在CMV感染的早期阶段，激活C型凝集素受体NKG 2C和NKG 2D的表达增加被IFN-γ分泌减少所抵消。结论：KIR/HLA基因型和NKG 2C、NKG 2D的表达可能在肾移植后NK细胞功能和抗CMV免疫中起重要作用。
Cytomegalovirus (CMV) infection is the most common viral complication after solid organ transplantation (SOT). Whilst current immunosuppression is known to impair antiviral-specific T-cell immunity in SOT, a potential role for natural killer (NK) cells not affected by immunosuppressive therapy remains to be determined. To address this, we compared the genotype of the NK immunoglobulin-like receptor (KIR) genes and their HLA cognate ligands to the rate of CMV infection in 196 kidney transplant recipients. We have shown that the absence of the HLA-C ligand for inhibitory KIR and the presence of activating KIR genes in the recipients were both associated with a lower rate of CMV infection after transplantation. In a cohort of 17 recipients with acute CMV infection, NK cells were phenotyped over a period of time after diagnosis by their expression profile of C-type lectin receptors and capacity to secrete IFN-gamma. The increased expression of the activating C-type lectin receptors NKG2C and NKG2D was paralleled by the decreased IFN-gamma secretion during the early phase of CMV infection. In conclusion, our findings suggest that KIR/HLA genotype and expression of NKG2C and NKG2D might play a significant role in regulating NK cell function and anti-CMV immunity after kidney transplantation.