Hadaya K, de Rham C, Bandelier C, Bandelier C, Ferrari-Lacraz S, Jendly S, Berney T, Buhler L, Kaiser L, Seebach J D, Tiercy J M, Martin P Y, Villard J
Service of Nephrology, Geneva University Hospital and Medical School, Switzerland.
Am J Transplant. 2008 Dec;8(12):2674-83. doi: 10.1111/j.1600-6143.2008.02431.x.
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.
巨细胞病毒(CMV)感染是实体器官移植(SOT)后最常见的病毒并发症。虽然已知目前的免疫抑制会损害SOT中抗病毒特异性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名肾移植受者中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。我们发现,受者中抑制性KIR的HLA-C配体缺失以及激活性KIR基因的存在均与移植后较低的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及其分泌IFN-γ的能力,在诊断后的一段时间内对NK细胞进行了表型分析。在CMV感染的早期阶段,激活性C型凝集素受体NKG2C和NKG2D表达的增加与IFN-γ分泌的减少同时出现。总之,我们的研究结果表明,KIR/HLA基因型以及NKG2C和NKG2D的表达可能在肾移植后调节NK细胞功能和抗CMV免疫中发挥重要作用。