Natural killer (NK) cell functions are regulated by diverse inhibitory and activating receptors, including killer cell immunoglobulin‐like receptors (KIR), which interact with human leukocyte antigen (HLA) class I molecules. Some KIR/HLA genetic combinations were reported associated with spontaneous clearance (SC) of hepatitis C virus (HCV) but with discordant results, possibly reflecting KIR and/or HLA gene polymorphism according to populations. KIR/HLA genetic combinations associated with both an exhaustive NK and T cell repertoire were investigated in a cohort of HIV–HCV co‐infected individuals with either SC (n = 68) or chronic infection (CI, n = 163) compared to uninfected blood donors [controls (Ctrl), n = 100]. Multivariate analysis showed that the HLA C2C2 environment was associated with SC only in European HIV–HCV co‐infected individuals [odds ratio (OR) = 4·30, 95% confidence interval = 1·57–12·25, P = 0·005]. KIR2D⁺ NK cell repertoire and potential of degranulation of KIR2DL1/S1⁺ NK cells were similar in the SC European cohort compared to uninfected individuals. In contrast, decreased frequencies of KIR2DS1⁺ and KIR2DL2⁺ NK cells were detected in the CI group of Europeans compared to SC and a decreased frequency of KIR2DL1/S1⁺ NK cells compared to controls. Regarding T cells, higher frequencies of DNAX accessory molecule‐1 (DNAM‐1)⁺ and CD57⁺ T cells were observed in SC in comparison to controls. Interestingly, SC subjects emphasized increased frequencies of KIR2DL2/L3/S2⁺ T cells compared to CI subjects. Our study underlines that the C2 environment may activate efficient KIR2DL1⁺ NK cells in a viral context and maintain a KIR2DL2/L3/S2⁺ mature T cell response in the absence of KIR2DL2 engagement with its cognate ligands in SC group of HCV–HIV co‐infected European patients.

中文翻译：

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HLA-C 环境对欧洲 HIV-HCV 合并感染者丙型肝炎自发清除的影响

自然杀伤 (NK) 细胞功能受多种抑制和激活受体的调节，包括杀伤细胞免疫球蛋白样受体 (KIR)，它们与人类白细胞抗原 (HLA) I 类分子相互作用。据报道，一些 KIR/HLA 基因组合与丙型肝炎病毒 (HCV) 的自发清除 (SC) 相关，但结果不一致，可能反映了不同人群的 KIR 和/或 HLA 基因多态性。KIR/HLA 基因组合与详尽的 NK 和T 细胞库 有关捐助者 [控制 (Ctrl), n = 100]。多变量分析表明，HLA C2C2 环境仅与欧洲 HIV-HCV 合并感染个体的 SC 相关[优势比 (OR) = 4·30, 95% 置信区间 = 1·57–12·25, P  = 0· 005]。与未感染个体相比，SC 欧洲队列中的KIR2D ⁺ NK 细胞库和 KIR2DL1/S1 ^{+ NK 细胞脱粒的可能性相似。}相反，与 SC 相比，在欧洲人的 CI 组中检测到KIR2DS1 ⁺和 KIR2DL2 ^{+ NK 细胞的频率降低，与对照组相比，KIR2DL1/S1 +} NK 细胞的频率降低。关于 T 细胞，DNAX 辅助分子-1 (DNAM-1) ⁺和 CD57的频率较高与对照相比，在 SC 中观察到^{+ T 细胞。}有趣的是，与 CI 受试者相比，SC 受试者强调 KIR2DL2/L3/S2 ^{+ T 细胞的频率增加。}我们的研究强调，C2 环境可能在病毒环境中激活有效的 KIR2DL1 ⁺ NK 细胞并在没有 KIR2DL2 与其同源配体参与的情况下维持 KIR2DL2/L3/S2 ⁺成熟 T 细胞反应。受感染的欧洲患者。