Ma Meichen, Wang Zhuo, Chen Xi, Tao Anfu, He Lei, Fu Shuai, Zhang Zining, Fu Yajing, Guo Chenxi, Liu Jing, Han Xiaoxu, Xu Junjie, Chu Zhenxing, Ding Haibo, Shang Hong, Jiang Yongjun
Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China.
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
Front Immunol. 2017 Sep 20;8:1176. doi: 10.3389/fimmu.2017.01176. eCollection 2017.
Natural killer (NK) cells are the first line of defense against pathogens of the immune system and also play an important role in resistance against HIV. The activating receptor NKG2C and the inhibitory receptor NKG2A co-modulate the function of NK cells by recognizing the same ligand, HLA-E. However, the role of NKG2A and NKG2C on viral set point and the prediction of HIV disease progression have been rarely reported. In this study, we determined the expression of NKG2C or NKG2A on the surface of NK cells from 22 individuals with primary HIV infection (PHI) stage and 23 HIV-negative normal control (NC) subjects. The CD4 T cell count and plasma level of HIV RNA in the infected individuals were longitudinally followed-up for about 720 days. The proportion of NKG2CNKG2A NK cells was higher in subjects from the low set point group and was negatively correlated with the viral load. In addition, strong anti-HIV activities were observed in NKG2C NK cells from the HIV-positive donors. Furthermore, a proportion of NKG2CNKG2A NK cells >35.45%, and a ratio of NKG2C/NKG2A >1.7 were predictive for higher CD4 T cell counts 720 days after infection. Collectively, the experimental results allow us to draw the conclusion that NKG2C NK cells might exert an antiviral effect and that the proportion of NKG2CNKG2A NK cells, and the ratio of NKG2C/NKG2A, are potential biomarkers for predicting HIV disease progression.
自然杀伤（NK）细胞是免疫系统抵御病原体的第一道防线，在抵抗HIV方面也发挥着重要作用。激活受体NKG2C和抑制受体NKG2A通过识别相同配体HLA-E共同调节NK细胞的功能。然而，NKG2A和NKG2C对病毒载量的作用以及对HIV疾病进展的预测鲜有报道。在本研究中，我们测定了22例原发性HIV感染（PHI）阶段个体和23例HIV阴性正常对照（NC）受试者NK细胞表面NKG2C或NKG2A的表达。对感染个体的CD4 T细胞计数和HIV RNA血浆水平进行了约720天的纵向随访。低病毒载量组受试者中NKG2C⁺NKG2A⁻ NK细胞的比例较高，且与病毒载量呈负相关。此外，在HIV阳性供体的NKG2C⁺ NK细胞中观察到较强的抗HIV活性。此外，NKG2C⁺NKG2A⁻ NK细胞比例>35.45%以及NKG2C/NKG2A比值>1.7可预测感染后720天较高的CD4 T细胞计数。总体而言，实验结果使我们得出结论，NKG2C⁺ NK细胞可能发挥抗病毒作用，NKG2C⁺NKG2A⁻ NK细胞的比例以及NKG2C/NKG2A比值是预测HIV疾病进展的潜在生物标志物。
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