CXCR5+ CD8+ T细胞在儿童传染性单核细胞增多症中的反应特点及临床价值
Responding Characteristics and Clinical Value of CXCR5+ CD8+ T Cells in Children with Infectious Mononucleosis
DOI: 10.12677/ACM.2023.1351140, PDF,    科研立项经费支持
作者: 薛 健*, 王建勇*, 辛 毅, 王晓莉, 李爱敏#:青岛大学附属烟台毓璜顶医院儿科,山东 烟台;张晓录, 谷钰峰:青岛大学附属烟台毓璜顶医院检验中心,山东 烟台;邢海燕:青岛大学附属烟台毓璜顶医院变态反应科,山东 烟台
关键词: CXCR5+ CD8+ T细胞EBV相关性IM流式细胞术EBV相关性肝损伤CXCR5+ CD8+ T Cells EBV-Associated IM Flow Cytometry EBV-Associated Liver Injury
摘要: 目的:本研究旨在探讨C-X-C趋化因子受体5型(CXCR5) CD8+ T细胞在儿童EBV相关传染性单核细胞增多症(IM)中的反应特点及临床价值。方法:采用流式细胞术及EB病毒(EBV)病原学检查分析入组儿童的外周血,同时收集临床资料进行统计分析。结果:EBV感染急性期CXCR5+ CD8+ T细胞绝对值计数显著增加,CXCR5+ CD8+ T/CD8+ T细胞比值、CD19+ B细胞的绝对值计数及CD19+ B细胞/LYM比值显著降低。CXCR5+ CD8+ T细胞绝对值计数与EBV DNA病毒载量、CD19+ B细胞绝对值计数呈负相关与肝损伤指标呈正相关。将EBV相关性IM急性期患儿以CXCR5+ CD8+ T细胞绝对值计数中位值分为高、低表达两组,高表达组中出现淋巴结肿大、肝脾肿大的几率明显高于低表达组。ROC曲线分析显示CXCR5+ CD8+ T细胞对儿童IM具有诊断价值,对于EBV相关肝损伤具有预测价值。结论:CXCR5+ CD8+ T细胞在EBV的急性感染中发挥了抗病毒作用,而其过度反应可能导致组织器官损伤。此外,CXCR5+ CD8+ T细胞可作为EBV相关IM诊断的诊断指标及EBV相关性肝损伤的预测指标。
Abstract: Objective: To investigate the response characteristics and clinical value of C-X-C chemokine receptor type 5 (CXCR5) CD8+ T cells in children with EBV-associated infectious mononucleosis (IM). Methods: Peripheral blood of the enrolled children was analyzed by flow cytometry and Epstein-Barr virus (EBV) etiology, and clinical data were collected for statistical analysis. Results: The absolute number of CXCR5+ CD8+ T cells increased significantly, the CXCR5+ CD8+ T/CD8+ T cell ratio, the absolute number of CD19+ B cells and the CD19+ B cell/LYM ratio decreased significantly in the acute stage of EBV infection. The absolute number of CXCR5+ CD8+ T cells was negatively correlated with EBV DNA load and absolute number of CD19+ B cells, and positively correlated with liver injury index. The children in the acute stage of EBV-associated IM were divided into high and low expression groups according to the median value of CXCR5+ CD8+ T cells absolute number. The probability of lym-phadenectasis, hepatosplenomegaly in the high expression group was significantly higher than that in the low expression group. ROC curve analysis showed that CXCR5+ CD8+ T cells had diagnostic value in EBV-associated IM, and had predictive value in EBV-related liver injury. Conclusion: CXCR5+ CD8+ T cells act as an antiviral role in acute infection of EBV, and their overreaction may lead to tis-sue and organ damage. In addition, CXCR5+ CD8+ T cells can be used as diagnostic indicators of EBV-associated IM and predictive indicators of EBV-associated liver injury.
文章引用:薛健, 王建勇, 张晓录, 谷钰峰, 邢海燕, 辛毅, 王晓莉, 李爱敏. CXCR5+ CD8+ T细胞在儿童传染性单核细胞增多症中的反应特点及临床价值[J]. 临床医学进展, 2023, 13(5): 8145-8155. https://doi.org/10.12677/ACM.2023.1351140

参考文献

[1] Luzuriaga, K. and Sullivan, J.L. (2010) Infectious Mononucleosis. The New England Journal of Medicine, 362, 1993-2000. [Google Scholar] [CrossRef
[2] Balfour, H.H., Dunmire, S.K. and Hogquist, K.A. (2015) Infectious Mononucleosis. Clinical & Translational Immunology, 4, e33. [Google Scholar] [CrossRef] [PubMed]
[3] Qiu, L., Wang, H., Yu, Q., et al. (2019) Protective Role of Follicular CXCR5(+)CD8(+) T Cells against Dengue Virus 2 Infection. International Journal of Infectious Diseases, 83, 12-19. [Google Scholar] [CrossRef] [PubMed]
[4] Jiang, H., Li, L., Han, J., et al. (2017) CXCR5(+) CD8(+) T Cells Indirectly Offer B Cell Help and Are Inversely Correlated with Viral Load in Chronic Hepatitis B Infection. DNA and Cell Biology, 36, 321-327. [Google Scholar] [CrossRef] [PubMed]
[5] Leong, Y.A., Chen, Y., Ong, H.S., et al. (2016) CXCR5(+) Follicular Cytotoxic T Cells Control viral Infection in B Cell Follicles. Nature Immunology, 17, 1187-1196. [Google Scholar] [CrossRef] [PubMed]
[6] Mylvaganam, G.H., Rios, D., Abdelaal, H.M., et al. (2017) Dynamics of SIV-Specific CXCR5+ CD8 T Cells during Chronic SIV Infection. Proceedings of the National Academy of Sciences of the United States of America, 114, 1976-1981. [Google Scholar] [CrossRef] [PubMed]
[7] Ayala, V.I., Deleage, C., Trivett, M.T., et al. (2017) CXCR5-Dependent Entry of CD8 T Cells into Rhesus Macaque B-Cell Follicles Achieved through T-Cell Engineering. Journal of Virology, 91, e02507-16. [Google Scholar] [CrossRef
[8] He, R., Hou, S., Liu, C., et al. (2016) Follicular CXCR5-Expressing CD8(+) T Cells Curtail Chronic Viral Infection. Nature, 537, 412-428. [Google Scholar] [CrossRef] [PubMed]
[9] Im, S.J., Hashimoto, M., Gerner, M.Y., et al. (2016) Defining CD8+ T Cells That Provide the Proliferative Burst after PD-1 Therapy. Nature, 537, 417-421. [Google Scholar] [CrossRef] [PubMed]
[10] Valentine, K.M. and Hoyer, K.K. (2019) CXCR5+ CD8 T Cells: Protective or Pathogenic? Frontiers in Immunology, 10, Article No. 1322. [Google Scholar] [CrossRef] [PubMed]
[11] Lam, J.K.P., Hui, K.F., Ning, R.J., et al. (2018) Emergence of CD4+ and CD8+ Polyfunctional T Cell Responses against Immunodominant Lytic and Latent EBV Antigens in Children with Primary EBV Infection. Frontiers in Microbiology, 9, Article No. 416. [Google Scholar] [CrossRef] [PubMed]
[12] Meckiff, B.J., Ladell, K., Mclaren, J.E., et al. (2019) Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4(+) T Cells. The Journal of Immunology, 203, 1276-1287. [Google Scholar] [CrossRef] [PubMed]
[13] Katz, B.Z., Reuter, C., Lupovitch, Y., et al. (2019) A Validated Scale for Assessing the Severity of Acute Infectious Mononucleosis. The Journal of Pediatrics, 209, 130-133. [Google Scholar] [CrossRef] [PubMed]
[14] Chen, L., Chen, X., Yao, W., et al. (2021) Dynamic Distribution and Clinical Value of Peripheral Lymphocyte Subsets in Children with Infectious Mononucleosis. Indian Journal of Pe-diatrics, 88, 113-119. [Google Scholar] [CrossRef] [PubMed]
[15] Quigley, M.F., Gonzalez, V.D., Granath, A., et al. (2007) CXCR5+ CCR7- CD8 T Cells Are Early Effector Memory Cells That Infiltrate Tonsil B Cell Follicles. European Jour-nal of Immunology, 37, 3352-3362. [Google Scholar] [CrossRef] [PubMed]
[16] Liu, J., Zhou, Y., Yu, Q., et al. (2015) Higher Frequency of CD4+CXCR5+ICOS+PD1+ T Follicular Helper Cells in Patients with Infectious Mononucleosis. Medicine (Baltimore), 94, e2061. [Google Scholar] [CrossRef
[17] Sallusto, F., Lenig, D., Förster, R., et al. (1999) Two Subsets of Memory T Lymphocytes with Distinct Homing Potentials and Effector Functions. Nature, 401, 708-712. [Google Scholar] [CrossRef] [PubMed]
[18] Roliński, J., Grywalska, E., Pyzik, A., et al. (2018) Interferon Alpha as Antivi-ral Therapy in Chronic Active Epstein-Barr Virus Disease with Interstitial Pneumonia—Case Report. BMC Infectious Diseases, 18, Article No. 190. [Google Scholar] [CrossRef] [PubMed]
[19] Castillo, J.J., Beltran, B.E., Miranda, R.N., et al. (2018) EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified: 2018 Update on Diagnosis, Risk-Stratification and Management. American Journal of Hematology, 93, 953-962. [Google Scholar] [CrossRef] [PubMed]
[20] Dunmire, S.K., Verghese, P.S. and Balfour, H.H. (2018) Primary Epstein-Barr Virus Infection. Journal of Clinical Virology, 102, 84-92. [Google Scholar] [CrossRef] [PubMed]
[21] Wu, Y., Ma, S., Zhang, L., et al. (2020) Clinical Manifesta-tions and Laboratory Results of 61 Children with Infectious Mononucleosis. Journal of International Medical Research, 48. [Google Scholar] [CrossRef] [PubMed]
[22] Fousteri, G. and Kuka, M. (2020) The Elusive Identity of CXCR5(+) CD8 T Cells in Viral Infection and Autoimmunity: Cytotoxic, Regulatory, or Helper Cells? Molecular Im-munology, 119, 101-105. [Google Scholar] [CrossRef] [PubMed]