Human regulatory T cells exert inhibitory function on CD4<sup>+</sup> effector T cells through interaction between herpes virus entry mediator and CD160

何跃; 韩容; 刘宏; 吴雄飞

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Human regulatory T cells exert inhibitory function on CD4⁺ effector T cells through interaction between herpes virus entry mediator and CD160

更新时间：2026-01-09

- Human regulatory T cells exert inhibitory function on CD4⁺ effector T cells through interaction between herpes virus entry mediator and CD160
- Journal of Army Medical University Vol. 33, Issue 10, Pages: 1012-1015(2011)
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  CLC： R392.12;R392.4;R392-33
- Published：2011
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何跃,韩容,刘宏,吴雄飞.Herpes virus entry mediator/CD160介导人调节性T细胞对CD4+效应性T细胞的抑制作用[J].陆军军医大学学报(原第三军医大学学报),2011,33(10):1012-1015.

　He Yue,Han Rong,Liu Hong,Wu Xiongfei.Human regulatory T cells exert inhibitory function on CD4+ effector T cells through interaction between herpes virus entry mediator and CD160[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(10):1012-1015.
何跃,韩容,刘宏,吴雄飞.Herpes virus entry mediator/CD160介导人调节性T细胞对CD4+效应性T细胞的抑制作用[J].陆军军医大学学报(原第三军医大学学报),2011,33(10):1012-1015. DOI：

　He Yue,Han Rong,Liu Hong,Wu Xiongfei.Human regulatory T cells exert inhibitory function on CD4+ effector T cells through interaction between herpes virus entry mediator and CD160[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(10):1012-1015. DOI：

摘要

目的研究HVEM、CD160在不同CD4

T细胞亚群，不同功能状态下的表达以及HVEM-CD160通路对CD4

CD25

调节性T细胞（regulatory T cell，Treg）免疫调节作用的影响。方法采用流式细胞分析术分别检测3例不同个体CD4

CD25

Tregs及CD4

CD25

T细胞在1 000 IU/ml人重组IL-2、与细胞数量1∶1的抗CD3/CD28 mAb包被磁珠的刺激下第0、3、5天HVEM或CD160的表达情况。采用1.25、2.5、5 μg/ml HSV

gD蛋白处理4例不同个体Treg，培养5 d 后，将处理的Treg与Teff在体外以1∶1混合并加入300 IU/ml IL-2及等量抗CD3/CD28 mAb包被磁珠，行混合淋巴细胞共培养，于培养结束前18 h加入

H-TdR，共培养7 d后检测各组细胞CPM增殖情况。5 μg/ml gD蛋白处理5例不同个体Treg后将其细胞浓度调整为5×10

并接种于6孔培养板内，加入500 IU/ml IL-2共培养7 d，行RT-PCR(Realtime PCR)分析Treg Foxp3基因表达。结果 HVEM在初始CD4

CD25

Tregs表面呈中度表达，平均表达率为42%，且随着Treg的活化其表达HVEM上调；CD160在初始CD4

CD25

T细胞表面呈低度表达，平均表达率仅7%，但伴随其活化，表达CD160有所上调。采用不同浓度HSV

gD蛋白处理Treg后2.5 μg/ml与5 μg/ml浓度组抑制CD4

CD25

T细胞增殖作用与空白对照组（276±35）相比明显下降，CPM值分别为(2 014±202)、(6 535±531)，差异具有统计学意义（P0.05），且具有浓度依赖性；RT-PCR分析发现Treg经5 μg/ml gD蛋白处理后Foxp3基因表达率下降，仅为空白对照组的48%，差异具有统计学意义（P0.01）。结论机体接受免疫刺激后Treg通过上调HVE

M表达与CD4

CD25

效应性T细胞（effective T cell，Teff）表面上调表达的受体CD160交联从而上调Treg Foxp3基因的表达，最终介导了Treg对Teff活化、增殖的抑制作用，HVEM-CD160通路对Treg免疫调节作用具有重要意义。

Abstract

Objective To study the expression of herpes virus entry mediator (HVEM) and CD160 in different CD4

T cell subsets under different function states and the influences of HVEM-CD160 pathway on CD4

CD25

regulatory T cells (Tregs). Methods Flow cytometry was used to detect HVEM and CD160 expression in CD4

CD25

Tregs and CD4

CD25

T cells from 3 different individuals at 0

and 5 d after stimulation by 1 000 IU/ml human IL-2 and magnetic beads (with equal number to the cells) coated with monoclonal antibodies against CD3 and CD28. Tregs from 4 different individuals were treated with HSV1 gD protein (0

1.25

2.5

and 5 μg/ml separately)

mixed with equivalent CD4

CD25

T cells and the magnetic beads and 300 IU/ml IL-2 in vitro

and cultured for 7 d.

H-TdR was added to the culture liquid 18 h before stopping the culture

and CPM value was detected. Tregs from 5 different individuals were treated with 5 μg/ml gD proteins

adjusted to a concentration of 5×10

transferred to a 6-well plate

and cultured with 500 IU/ml IL-2 for 7 d. Treg Foxp3 gene expression was detected by real-time RT-PCR. Results HVEM expression was at a medium level on naive CD4

CD25

Treg surfaces with an average expression rate of 42%

and was up-regulated along with Treg activation. CD160 expression was at a low level on naive CD4

CD25

T cell surfaces with an average expression rate of 7%

and was up-regulated along with CD4

CD25

T cell activation. Tregs treated with 2.5 and 5 μg/ml HSV

gD protein had significantly lowered and concentration-dependent inhibition effects on CD4

CD25

T cell proliferation (average CPM value 2 014±202 and 6 535±531) as compared with Tregs without treatment (average CPM value 276±35

P0.05). RT-PCR results showed that Tregs treated with 5 μg/ml gD protein had a decreased Foxp3 gene expression rate

only 48% that of Tregs without treatment (P0.01). Conclusion After immunostimulation

up-regulated HVEM in activated Tregs and up-regulated CD160 in activated CD4

CD25

effector T cells (Teffs) interact to promote Treg Foxp3 gene expression

resulting in Treg’s inhibition effects on Teff activation and proliferation. HVEM-CD160 pathway is important for Treg’s inhibitory function.

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Human regulatory T cells exert inhibitory function on CD4+ effector T cells through interaction between herpes virus entry mediator and CD160

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摘要

Abstract

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references

Human regulatory T cells exert inhibitory function on CD4⁺ effector T cells through interaction between herpes virus entry mediator and CD160