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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
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Abstract:
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。
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.
| [1] | Luzuriaga, K. and Sullivan, J.L. (2010) Infectious Mononucleosis. The New England Journal of Medicine, 362, 1993-2000. https://doi.org/10.1056/NEJMcp1001116 |
| [2] | Balfour, H.H., Dunmire, S.K. and Hogquist, K.A. (2015) Infectious Mononucleosis. Clinical & Translational Immunology, 4, e33. https://doi.org/10.1038/cti.2015.1 |
| [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. https://doi.org/10.1016/j.ijid.2019.03.024 |
| [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.
https://doi.org/10.1089/dna.2016.3571 |
| [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. https://doi.org/10.1038/ni.3543 |
| [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. https://doi.org/10.1073/pnas.1621418114 |
| [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.
https://doi.org/10.1128/JVI.02507-16 |
| [8] | He, R., Hou, S., Liu, C., et al. (2016) Follicular CXCR5-Expressing CD8(+) T Cells Curtail Chronic Viral Infection. Nature, 537, 412-428. https://doi.org/10.1038/nature19317 |
| [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. https://doi.org/10.1038/nature19330 |
| [10] | Valentine, K.M. and Hoyer, K.K. (2019) CXCR5+ CD8 T Cells: Protective or Pathogenic? Frontiers in Immunology, 10, Article No. 1322. https://doi.org/10.3389/fimmu.2019.01322 |
| [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. https://doi.org/10.3389/fmicb.2018.00416 |
| [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.
https://doi.org/10.4049/jimmunol.1900377 |
| [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. https://doi.org/10.1016/j.jpeds.2019.01.035 |
| [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.
https://doi.org/10.1007/s12098-020-03319-7 |
| [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.
https://doi.org/10.1002/eji.200636746 |
| [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.
https://doi.org/10.1097/MD.0000000000002061 |
| [17] | Sallusto, F., Lenig, D., F？rster, R., et al. (1999) Two Subsets of Memory T Lymphocytes with Distinct Homing Potentials and Effector Functions. Nature, 401, 708-712. https://doi.org/10.1038/44385 |
| [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.
https://doi.org/10.1186/s12879-018-3097-6 |
| [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. https://doi.org/10.1002/ajh.25112 |
| [20] | Dunmire, S.K., Verghese, P.S. and Balfour, H.H. (2018) Primary Epstein-Barr Virus Infection. Journal of Clinical Virology, 102, 84-92. https://doi.org/10.1016/j.jcv.2018.03.001 |
| [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. https://doi.org/10.1177/0300060520924550 |
| [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.
https://doi.org/10.1016/j.molimm.2020.01.007 |
