The Role of Foxp3, CD4+CD25+ Regulatory T Cells on the Pathogenesis of Infectious Mononucleosis in Children

doi:10.3877/cma.j.issn.1673-5250.2013.02.008

Objective

To investigate the role of CD₄⁺CD₂₅⁺ regulatory T cells(Treg) and transcription factor Foxp3 on the pathogenesis of infectious mononucleosis(IM) in children.

Methods

From April 2010 to January 2011, 70 blood samples from 35 IM children(2 samples each person) were included into this study, and divided into IM acute stage group(n=35) and IM recovery stage group(n=35) according to the different disease periods.Meanwhile, 35 blood samples which taken from health children (1 sample each person) were chosen as control group(n=35). The expression of T lymphocyte subsets CD₃⁺, CD₃⁺CD₄⁺, CD₃⁺CD₈⁺, CD₄⁺CD₂₅⁺ Treg and Foxp3 mRNA were compared among three groups. There was no significant difference in age and sex distribution between IM patients and health chirdren (P>0.05). The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Sichuan Province People's Hospital.Informed consent was obtained from each parents.

Results

There had significant differences among three groups in relative expression levels of CD₃⁺, CD₃⁺CD₄⁺, CD₃⁺CD₈⁺, CD₄⁺CD₂₅⁺ Treg (P<0.01). The relative levels of Foxp3 mRNA in IM acute stage group(2.82±0.90) were obviously lower than those of IM recovery stage group(4.11±1.37) and control group (4.65±1.23) (P<0.01). There was no significant difference between IM recovery stage group and control group(P>0.05). A significant positive correlation was found between CD₄⁺CD₂₅⁺ Treg and expression of Foxp3 mRNA in IM acute stage group(r=0.823, P<0.05).

Conclusions

There is functional disorder of T lymphocyte subsets at acute stage of IM in children. The relative expression levels of CD₄⁺CD₂₅⁺ Treg were reduced, and their special transcription factor Foxp3 mRNA were decreased, which led to the insufficient immunosuppressive effects that may be one of the important reasons of the immune imbalance.

Key words: Foxp3, CD₄⁺CD₂₅⁺ regulatory T cell, infectious mononucleosis, child

表1 3组CD₃⁺，CD₃⁺ CD₄⁺，CD₃⁺CD₈⁺，CD₄⁺/CD₈⁺的相对表达水平比较(±s)

Table 1 Comparison of the relative expression levels of CD₃⁺，CD₃⁺CD₄⁺，CD₃⁺CD₈⁺，CD₄⁺/CD₈⁺ among three groups(±s)

组别	n	CD₃⁺	CD₃⁺ CD₄⁺	CD₃⁺CD₈⁺	CD₄⁺/CD₈⁺
IM急性期组	35	80.66±4.88	16.53±5.55	62.71±8.76	0.26±0.12
IM恢复期组	35	74.25±7.33	29.89±6.03	42.25±7.33	0.71± 0.19
对照组	35	63.04±5.51	37.98±4.20	27.71±6.52	1.37±0.45
F		49.98	107.23	139.82	120.53
P		<0.01	<0.01	<0.01	<0.01

表1 3组CD₃⁺，CD₃⁺ CD₄⁺，CD₃⁺CD₈⁺，CD₄⁺/CD₈⁺的相对表达水平比较(±s)

Table 1 Comparison of the relative expression levels of CD₃⁺，CD₃⁺CD₄⁺，CD₃⁺CD₈⁺，CD₄⁺/CD₈⁺ among three groups(±s)

组别	n	CD₃⁺	CD₃⁺ CD₄⁺	CD₃⁺CD₈⁺	CD₄⁺/CD₈⁺
IM急性期组	35	80.66±4.88	16.53±5.55	62.71±8.76	0.26±0.12
IM恢复期组	35	74.25±7.33	29.89±6.03	42.25±7.33	0.71± 0.19
对照组	35	63.04±5.51	37.98±4.20	27.71±6.52	1.37±0.45
F		49.98	107.23	139.82	120.53
P		<0.01	<0.01	<0.01	<0.01

表2 3组Foxp3 mRNA，CD₄⁺CD₂₅⁺ Treg相对表达水平比较(±s)

Table 2 Comparison of the relative expression levels of Foxp3 mRNA, CD₄⁺CD₂₅⁺ Treg among three groups(±s)

组别	n	Foxp3 mRNA	CD₄⁺CD₂₅⁺ Treg
IM急性期组	35	2.82±0.90	2.38±1.32
IM恢复期组	35	4.11±1.37	6.81±1.84
对照组	35	4.65±1.23	7.85±1.97
F		23.92	30.61
P		<0.01	<0.01

表2 3组Foxp3 mRNA，CD₄⁺CD₂₅⁺ Treg相对表达水平比较(±s)

Table 2 Comparison of the relative expression levels of Foxp3 mRNA, CD₄⁺CD₂₅⁺ Treg among three groups(±s)

组别	n	Foxp3 mRNA	CD₄⁺CD₂₅⁺ Treg
IM急性期组	35	2.82±0.90	2.38±1.32
IM恢复期组	35	4.11±1.37	6.81±1.84
对照组	35	4.65±1.23	7.85±1.97
F		23.92	30.61
P		<0.01	<0.01

图1 CD₄⁺CD₂₅⁺Treg与Foxp3 mRNA的相关性分析图

Figure 1 The scatter of CD₄⁺CD₂₅⁺Treg and Foxp3 mRNA

[1]	Michelow P, Wright C, Pantanowitz LA.Review of the cytomorphology of epstein-barr virus-associated malignancies[J].Acta Cytol, 2012, 56(1):1-14.
[2]	Okano M, Gross TG.Acute or chronic life-threatening diseases associated with Epstein-Barr virus infection[J].Am J Med Sci, 2011, 343(6):1-7.
[3]	Ambinder RF. Epstein-Barr virus and Hodgkin lymphoma[J]. Hematol Am Soc Hematol Educ Program, 2007:204-209.
[4]	Mueller NE, Lennette ET, Dupnik K, et al. Antibody titers against EBNA1 and EBNA2 in relation to Hodgkin lymphoma and history of infectious mononucleosis[J]. Int J Cancer, 2012, 130(12):2886-2891.
[5]	Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD₂₅). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J]. J Immunol, 1995, 155(3):1151-1164.
[6]	Xie ZD. Clinical features and diagnositc criteria of infectious mononucleosis associated with Epstein-Barr virus infection in children[J]. J Appl Clin Pediatr, 2007, 22(22):1759-1760.
[7]	Piccirillo CA.Regulatory T cells in health anddisease[J].Cytokine, 2008, 43(3):395-401.
[8]	Wingate PJ, McAulay KA, Anthony IC, et al. Regulatory T cell activity in primary and persistent Epstein-Barr virus infection[J]. J Med Virol, 2009, 81:870-877.
[9]	Wilczynki JR, Radwan M, Kalinka J.The characterization and role of regulatory T cells in immune reactions[J].Front Biosci, 2008, 1(13):2266-2227.
[10]	Sharma R, Zheng L, Deshmukh US, et al. A Regulatory T Cell-dependent novel function of CD₂₅⁺ controlling memory CD₈⁺ T cell homeostasis[J].J Immunol, 2007, 178(3):1251-1125.
[11]	Cao X, Cai SF, Fehniger TA, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance[J]. Immunity, 2007, 279(4):635-646.
[12]	Pandiyan P, Zheng L, Ishihara S, et al.CD₄⁺CD₂₅⁺Foxp3^＋ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD₄⁺ T cells[J]. Nat Immunol, 2007:1353-1362.
[13]	Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance[J]. Cell, 2008, 133(5):775-787.
[14]	Chow YH, Chang HW, Sia R, et al.Tonsillar CD₄⁺Foxp3^＋ T-regulatory cell dynamics in primary EBV infection[J].Immunol Res, 2011, 50(1):97-101.
[15]	Ziegler SF. Foxp3 of mice and men[J].Annu Rev Immunol, 2006, 24:209-226.
[16]	Fontenot JD, Rasmussen JP, Williams LM, et al.Regulatory T cell lineage specification by the forkhead transcription factor Foxp3[J]. Immunity, 2005, 22(3):329-341.
[17]	Wang Q, Dong W, Fang J, et al. Roles of CD₄⁺CD₂₅⁺ T regulatory cells in acute infectious mononucleosis in children[J].J Appl Clin Pediatr, 2009, 24(22):1722-1728.
[18]	Qiu LN, Zhou YL, Luo XM, et al.Study of the inhibition effects of CD₄⁺CD₂₅⁺ /highCD₁₂₇low on the immortalized cells in children with infectious mononucleosis[J]. Chin J Microbiol Immunol, 2009, 29(7):623-626.
[19]	Cao YD, Nie SD, Deng ZH, et al. Dynamic analysis of T lymphocyte subsets in children with infectious mononucleosis[J]. Int J Lab Med, 2012, 33(1):20-22.
[20]	Margaret F, Callan C. The evolution of antigen-specific CD₈ T cell responses after matural primary infection of humans with Epstein-Barr virus[J].Viral Immunol, 2003, 6(1):3-16.
[21]	Precopio ML, Sullivan JL, Willard C, et al. Differential kinetics and specificity of EBV-specific CD₄⁺ and CD₈⁺ T cells during primary infection[J].J Immunol, 2003, 170(5):2590-2598.
[22]	Ren SH, Wang Q, Fang J, et al. Dynamic changes of T lymphocyte subset and B cells in children with infectious mononucleosis caused by epstein-barr virus[J/CD].Chin J Obstet Gynecol Pediatr:Electron Ed, 2009, 5(5):7-1.

[1]	Xuan Zhang, Yutong Ma, Yuqian Miao, Yun Zhang, Shiwen Wu, Xiaochu Dang, Yingying Chen, Zhaoming Zhong, Xuejuan Wang, Miao Hu, Yanfeng Sun, Xiuzhu Ma, Faqin Lyu, Haiyan Kou. Ultrasound assessment of diaphragm function in pediatric patients with Duchenne muscular dystrophy[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(10): 1068-1073.
[2]	Baofu Zhang, Jin Yu, Jingjing Ye, Jiangen Yu, Xiaohui Ma, Xiwang Liu. Echocardioimagedata diagnosis of anomalous pulmonary venous connection caused by congenital malposition of the septum primum[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(10): 1074-1080.
[3]	Dan Han, Ting Wang, Huan Xiao, Lirong Zhu, Jingyu Chen, Yi Tang. Diagnostic value of contrast enhanced ultrasound versus contrast enhanced computed tomography in benign and malignant liver lesions in children[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(09): 939-944.
[4]	Tingting Liu, Yanbing Lin, Shan Wang, Murong Chen, Zijian Tang, Dongling Dai, Bei Xia. Evaluation of metabolic dysfunction-associated fatty liver disease in children by ultrasound-guided attenuation parameter[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(08): 787-794.
[5]	Yuhan Zhou, Huan Xiao, Chunjiang Yang, Juan Zhou, Lirong Zhu, Juan Xu, Fangting Mou. Diagnostic value of ultrasound in children with temporary hip synovitis[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(08): 795-800.
[6]	Jiu Wang, Jun Chen, Xia Zhu, Yangjin Mima, Sheng Zhao, Xinlin Chen, Jianhua Li, Shuang Wang. Effect of implementing fetal systemic ultrasound screening in Material and Child Health Hospital of Shannan[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(07): 728-733.
[7]	Jie Mi, Chen Chen, Jialing Li, Haina Pei, Hengbo Zhang, Fei Li, Dongjie Li. Analysis of the characteristics of children's head and face trauma[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2023, 18(06): 511-515.
[8]	Tao Ma, Chunwei Ye, Tao Liu, Wenxi Peng, Zhipeng Li. Comparison of laparoscopic and open disconnected pyeloplasty in the treatment of ureteropelvic junction obstruction in children[J]. Chinese Journal of Endourology(Electronic Edition), 2023, 17(06): 605-610.
[9]	Lei Wang, Shaohua Wang, Haizhen Niu, Tengfei Yin. Application of early warning intervention based on risk assessment in perioperative nursing of children with inguinal hernia[J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2023, 17(06): 768-772.
[10]	Fang Li, Rui Xu, Yangyang Li, Xiuquan Shi. Application of the concept of evidence-based medicine in children with inguinal hernia[J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2023, 17(06): 782-786.
[11]	Lei Lyu, Xiao Feng, Kaiming He, Kaining Zeng, Qing Yang, Haijin Lyu, Huimin Yi, Shuhong Yi, Yang Yang, Binsheng Fu. Value of revised King's score in evaluation of live transplantation timing for children with acute liver failure due to Wilson's disease and literature review[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(06): 661-668.
[12]	Zehui Huang, Jiexian Liang, Wei Zeng. Application of dexmedetomidine combined with esketamine in painless gastroscopy in children[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 510-513.
[13]	Xiangyu Zhu, Jianmei Wang, Hui Zhang, Hongying Ye. Correlation analysis between left ventricular function parameters and liver cirrhosis using non-invasive left ventricular pressure-strain cycle[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 494-498.
[14]	Shaohong Zhuo, Xiuling Lin, Cuimei Zhou, Weilian Xiong, Xingzao Ma. Application value of CD64 index combined with serum SAA/CRP and PCT in the diagnosis of children with infectious gastrointestinal diseases[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 505-509.
[15]	Jing Li, Lingling Zhang, Wei Xing. Value of concept of interest induction before anesthesia induction in pediatric surgery and its effect on family satisfaction[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(07): 812-817.

Viewed

Full text

Abstract

Please choose a citation manager

Content to export

The Role of Foxp3, CD₄⁺CD₂₅⁺ Regulatory T Cells on the Pathogenesis of Infectious Mononucleosis in Children

模态框（Modal）标题

Please choose a citation manager

Content to export

The Role of Foxp3, CD4+CD25+ Regulatory T Cells on the Pathogenesis of Infectious Mononucleosis in Children

The Role of Foxp3, CD₄⁺CD₂₅⁺ Regulatory T Cells on the Pathogenesis of Infectious Mononucleosis in Children