CD4+CD25+调节性T细胞及Foxp3在儿童传染性单核细胞增多症发病中的作用

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

目的

探讨CD₄⁺CD₂₅⁺调节性T细胞(Treg)及其转录因子Foxp3在儿童传染性单核细胞增多症(IM)发病中的作用。

方法

选择2010年4月至2011年1月于四川省人民医院诊治的35例IM患儿的外周静脉血标本(每例患儿分别采集2个)为研究对象，并按照标本采集时期分为IM急性期组(n＝35)和IM恢复期组(n＝35)。选择同期于本院儿童保健门诊进行常规体检的35例健康儿童的外周静脉血标本(每例儿童采集1个)为对照组(本研究遵循的程序符合本院人体试验委员会所制定的伦理学标准，得到该委员会批准，分组征得受试对象监护人的知情同意，并与之签署临床研究知情同意书)。分别检测3组血样标本中CD₃⁺，CD₃⁺CD₄⁺，CD₃⁺CD₈⁺，CD₄⁺CD₂₅⁺ Treg表达率及Foxp3 mRNA水平，并进行统计学分析。IM患儿与健康儿童的年龄及性别分布比较，差异无统计学意义(P>0.05)。

结果

IM急性期组外周血CD₃⁺，CD₃⁺CD₄⁺，CD₃⁺CD₈⁺，CD₄⁺/CD₈⁺和CD₄⁺CD₂₅⁺ Treg测定结果分别与IM恢复期组和对照组比较，差异有统计学意义(P<0.01)；IM急性期组Foxp3 mRNA表达水平显著降低，分别与IM恢复期组和对照组比较，差异也有统计学意义(P<0.01)，IM恢复期组与对照组比较，差异无统计学意义(P>0.05)。IM急性期组CD₄⁺CD₂₅⁺ Treg与Foxp3 mRNA表达呈正相关关系(r＝0.823，P<0.05)。

结论

IM急性期存在明显免疫失衡，即CD₃⁺CD₈⁺明显增高，CD₃⁺CD₄⁺及CD₄⁺/CD₈⁺明显降低，其免疫失衡原因可能是由于CD₄⁺CD₂₅⁺ Treg数量降低及其转录因子Foxp3表达下调导致的免疫抑制功能不足所致。

关键词: Foxp3, CD₄⁺CD₂₅⁺调节性T细胞, 传染性单核细胞增多症, 儿童

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

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

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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