Department of Pathology and Immunology, Baylor College of Medicine, Houston, Tex; Center for Human Immunobiology, Texas Children's Hospital, Houston, Tex.
Center for Human Immunobiology, Texas Children's Hospital, Houston, Tex; Department of Pediatrics, Baylor College of Medicine, Houston, Tex.
J Allergy Clin Immunol. 2019 Jul;144(1):294-303.e13. doi: 10.1016/j.jaci.2018.11.052. Epub 2019 Feb 5.
Chronic HIV infection is known to trigger a population redistribution and alteration in the functional capacity of natural killer (NK) cells. Because of improved antiretroviral treatments, there are rising numbers of adolescents and young adults worldwide who are living with HIV infection since birth.
We sought to determine how NK-cell phenotypic and functional subsets are altered in treated pediatric patients.
NK cells were contrasted among 29 HIV-unexposed and uninfected controls (5-19 years), 23 HIV-exposed but uninfected patients (3-19 years), and 25 HIV-infected patients (3-19 years) using multiparametric flow cytometry.
Although most NK-cell markers did not differ, activating receptors such as NKp46, DNAX accessory molecule-1, and NKG2C and stimulatory receptors such as CD2 and CD11c were expressed by a higher frequency of NK cells in HIV-infected patients than in controls. Interestingly, there were less differences between HIV-infected and HIV-exposed but uninfected children. There was an inverse relationship between CD4/CD8 T-cell ratio (as a marker of disease progression) and CD11c and NKG2C frequency and CD69 upregulation on stimulation among HIV-infected patients.
A chronic NK-cell activation phenotype persists in HIV-infected children receiving antiretroviral therapy and is associated with declining CD4/CD8 T-cell ratios. A lower CD4/CD8 T-cell ratio was associated with higher baseline granzyme B (P = .0068; R = 0.29) and degranulation potential (P = .022; R = 0.22) in stimulated NK cells. Thus, NK cells in HIV-infected children receiving treatment have reduced functional potential and an activated phenotype that distinguishes them from uninfected children.
慢性 HIV 感染已知会引发自然杀伤 (NK) 细胞的群体再分布和功能能力改变。由于抗逆转录病毒治疗的改善，全世界有越来越多的青少年和年轻人从出生起就感染了 HIV。
我们旨在确定 NK 细胞表型和功能亚群在接受治疗的儿科患者中是如何改变的。
我们使用多参数流式细胞术对比了 29 名未接触 HIV 且未感染的对照组（5-19 岁）、23 名接触过 HIV 但未感染的患者（3-19 岁）和 25 名 HIV 感染患者（3-19 岁）的 NK 细胞。
尽管大多数 NK 细胞标志物没有差异，但在 HIV 感染患者中，NK 细胞表达更高频率的激活受体，如 NKp46、DNAX 辅助分子-1 和 NKG2C，以及刺激受体，如 CD2 和 CD11c。有趣的是，HIV 感染和接触过 HIV 但未感染的儿童之间的差异较小。在 HIV 感染患者中，CD4/CD8 T 细胞比值（作为疾病进展的标志物）与 CD11c 和 NKG2C 频率以及刺激后 CD69 上调呈负相关。
在接受抗逆转录病毒治疗的 HIV 感染儿童中，持续存在慢性 NK 细胞激活表型，与 CD4/CD8 T 细胞比值下降有关。较低的 CD4/CD8 T 细胞比值与刺激后 NK 细胞中更高的基础 granzyme B（P=0.0068；R=0.29）和脱颗粒潜力（P=0.022；R=0.22）相关。因此，接受治疗的 HIV 感染儿童的 NK 细胞功能潜力降低，表现出激活表型，这使其与未感染儿童区分开来。
