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在患有活动性巨细胞病毒感染的肾移植患者中,Th22 细胞和 IL-22 细胞因子的频率降低。

Decreased frequency of Th22 cells and IL-22 cytokine in kidney transplant patients with active cytomegalovirus infection.

机构信息

Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran.

Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

BMC Immunol. 2023 Jul 4;24(1):18. doi: 10.1186/s12865-023-00555-2.

DOI:10.1186/s12865-023-00555-2
PMID:37403036
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10318775/
Abstract

BACKGROUND

The immunity of CD4 T cell subsets against human cytomegalovirus (HCMV) is considerable due to their essential role in controlling the infection in transplant individuals. Previously explained CD4 subsets such as T helper (Th) 1 have been proven to have a protective role against HCMV infection, while the role of the recently identified Th22 subset has not been described yet. Here, the frequency changes of Th22 cells and the IL-22 cytokine production were investigated in kidney transplant recipients with and without HCMV infection.

METHODS

Twenty kidney transplant patients and ten healthy controls were enrolled in this study. Patients were categorized into HCMV + and HCMV- groups based on the HCMV DNA real-time PCR results. After isolating CD4 T cells from PBMCs, the phenotype (CCR6CCR4CCR10) and cytokine profile (IFN-γIL-17IL-22) of Th22 cells were analyzed by flow cytometry. The gene expression of Aryl Hydrocarbon Receptor (AHR) transcription factor was analyzed by real-time PCR.

RESULTS

The phenotype frequency of these cells was lower in recipients with infection than in those without infection and healthy controls (1.88 ± 0.51 vs. 4.31 ± 1.05; P = 0.03 and 4.22 ± 0.72; P = 0.01, respectively). A lower Th22 cytokine profile was observed in patients with infection than in the two other groups (0.18 ± 0.03 vs. 0.20 ± 0.03; P = 0.96 and 0.33 ± 0.05; P = 0.04, respectively). AHR expression was also lower in patients with active infection.

CONCLUSIONS

Overall, this study for the first time suggests that the reduced levels of Th22 subset and IL-22 cytokine in patients with active HCMV infection might indicate the protective role of these cells against HCMV.

摘要

背景

CD4 T 细胞亚群对人巨细胞病毒(HCMV)的免疫具有相当大的作用,因为它们在控制移植个体中的感染方面发挥着重要作用。先前已解释的 CD4 亚群,如辅助性 T 细胞(Th)1,已被证明具有抵抗 HCMV 感染的保护作用,而最近发现的 Th22 亚群的作用尚未描述。在这里,研究了肾移植受者中存在和不存在 HCMV 感染时 Th22 细胞的频率变化和 IL-22 细胞因子的产生。

方法

本研究纳入了 20 名肾移植患者和 10 名健康对照者。根据 HCMV DNA 实时 PCR 结果,将患者分为 HCMV+和 HCMV-组。从 PBMC 中分离 CD4 T 细胞后,通过流式细胞术分析 Th22 细胞的表型(CCR6CCR4CCR10)和细胞因子谱(IFN-γIL-17IL-22)。通过实时 PCR 分析芳香烃受体(AHR)转录因子的基因表达。

结果

与未感染和健康对照组相比,感染患者的这些细胞表型频率较低(1.88±0.51 对 4.31±1.05;P=0.03 和 4.22±0.72;P=0.01)。与其他两组相比,感染患者的 Th22 细胞因子谱较低(0.18±0.03 对 0.20±0.03;P=0.96 和 0.33±0.05;P=0.04)。活跃感染患者的 AHR 表达也较低。

结论

总的来说,这项研究首次表明,活跃 HCMV 感染患者 Th22 亚群和 IL-22 细胞因子水平降低可能表明这些细胞对 HCMV 具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450b/10318775/2292014d3824/12865_2023_555_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450b/10318775/df05985cea2c/12865_2023_555_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450b/10318775/d5aae6122458/12865_2023_555_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450b/10318775/ad247427582d/12865_2023_555_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450b/10318775/2292014d3824/12865_2023_555_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450b/10318775/df05985cea2c/12865_2023_555_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450b/10318775/d5aae6122458/12865_2023_555_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450b/10318775/ad247427582d/12865_2023_555_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450b/10318775/2292014d3824/12865_2023_555_Fig4_HTML.jpg

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Loss of CCR7 Expression.CCR7表达缺失。
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Th22 Cells Are a Major Contributor to the Mycobacterial CD4 T Cell Response and Are Depleted During HIV Infection.Th22 细胞是分枝杆菌 CD4 T 细胞反应的主要贡献者,并在 HIV 感染期间被耗尽。
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