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宫内巨细胞病毒感染新生儿中 CD8CD28+Treg 和 γδ-T 细胞的变化:一例报告。

Changes of CD8CD28 Tregs and Gamma-Delta-T-cells in a Neonate with Intrauterine Cytomegalovirus Infection: A Case Report.

机构信息

Department of Laboratory Medicine, Shenzhen Baoan Women's and Children's Hospital, Shenzhen, China.

Department of Neonatology, Shenzhen Baoan Women's and Children's Hospital, Shenzhen, China.

出版信息

BMC Pediatr. 2024 Sep 16;24(1):587. doi: 10.1186/s12887-024-05051-z.

DOI:10.1186/s12887-024-05051-z
PMID:39285316
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11403953/
Abstract

BACKGROUND

Congenital cytomegalovirus (cCMV) infection can lead to a range of adverse outcomes. The majority of cCMV neonates with clinical symptoms are infected postnatally; however, established cases of intrauterine infection are uncommon, resulting in a paucity of reports on clinical findings and lymphocytes expression in CMV-infected neonates.

CASE PRESENTATION

We followed a neonate with cCMV infection from the onset of hospitalization to several months of follow-up. This infant was intrauterine CMV-positive in the amniotic fluid of the mother at 21 weeks' gestation and received intravenous ganciclovir infusion and sequential oral valganciclovir after birth. The typical clinical signs manifested in the nervous system, liver, and peripheral blood and were documented during the hospitalizaion period and up to the follow-up visit. Flow cytometry was employed to examine the expression of T cells, their subsets, and the associated cytokines in peripheral blood samples at various time points. The flow data for the cCMV neonate were compared with those of the controls at each time point. Following treatment, clinical symptoms improved and the infant became CMV negative. However, developmental delays occurred later in life. The proportion of CD8CD28 Tregs in the peripheral blood of the neonate with congenital CMV infection was higher than that in the controls at the three time points. The expression levels of perforin and granzyme B secreted by γδ T cells (Vδ1 and Vδ2 T cells), increased during the course of hospitalization until follow-up and were higher than those in the controls at the three time points.

CONCLUSIONS

Despite the alleviation of clinical symptoms, developmental delay in later life remains inevitable in this intrauterine cCMV neonate. CD8CD28 Tregs and Vδ1 and Vδ2 T cells secreting perforin and granzyme B may be involved in congenital CMV infection, although this hypothesis requires validation in a larger study. This report may contribute to our understanding of the effect of current treatment and the immune status of intrauterine cCMV-infected neonates.

摘要

背景

先天性巨细胞病毒(cCMV)感染可导致一系列不良后果。大多数有临床症状的 cCMV 新生儿是出生后感染的;然而,宫内感染的确诊病例并不常见,因此关于 CMV 感染新生儿的临床发现和淋巴细胞表达的报道很少。

病例介绍

我们对一例先天性巨细胞病毒感染的新生儿从住院开始到随访了几个月。这名婴儿在 21 周妊娠时母亲的羊水呈 CMV 阳性,出生后接受静脉更昔洛韦输注和序贯口服缬更昔洛韦治疗。在住院期间和随访期间,记录了神经系统、肝脏和外周血的典型临床表现。采用流式细胞术检测外周血样本中 T 细胞及其亚群和相关细胞因子的表达情况,在不同时间点与对照组进行比较。治疗后,临床症状改善,婴儿转为 CMV 阴性,但后来出现发育迟缓。先天性 CMV 感染新生儿外周血中 CD8CD28 Tregs 的比例在三个时间点均高于对照组。γδ T 细胞(Vδ1 和 Vδ2 T 细胞)分泌的穿孔素和颗粒酶 B 的表达水平在住院期间持续增加,直至随访,并在三个时间点均高于对照组。

结论

尽管临床症状有所缓解,但宫内先天性 CMV 感染的新生儿在以后的生活中仍不可避免地会出现发育迟缓。CD8CD28 Tregs 和分泌穿孔素和颗粒酶 B 的 Vδ1 和 Vδ2 T 细胞可能参与先天性 CMV 感染,但这一假设需要更大规模的研究来验证。本报告有助于我们了解当前治疗的效果和宫内先天性 CMV 感染新生儿的免疫状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd7/11403953/0f1e9e508742/12887_2024_5051_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd7/11403953/feffa3a8b06b/12887_2024_5051_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd7/11403953/0f1e9e508742/12887_2024_5051_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd7/11403953/feffa3a8b06b/12887_2024_5051_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd7/11403953/0f1e9e508742/12887_2024_5051_Fig2_HTML.jpg

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本文引用的文献

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The emerging roles of γδ T cells in cancer immunotherapy.γδ T细胞在癌症免疫治疗中的新作用。
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A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.
巨细胞病毒免疫球蛋白预防先天性巨细胞病毒感染的临床试验
N Engl J Med. 2021 Jul 29;385(5):436-444. doi: 10.1056/NEJMoa1913569.
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Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC).巨细胞病毒与炎症性肠病(IBD),特别关注与溃疡性结肠炎(UC)的关联。
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Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis.巨细胞病毒血清阳性的自身免疫性关节炎患者中,CD8 + T细胞产生显著的γ干扰素反应。
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