Tissue-resident CD8+T memory cells with unique properties are present in human decidua during early pregnancy
Tissue-resident CD8+T memory cells with unique properties are present in human decidua during early pregnancy
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妊娠早期人类蜕膜中存在具有独特性质的组织驻留 CD8( )T 记忆细胞
DOI：
10.1111/aji.13254
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发表时间：
2020-05-23
影响因子：
3.6
通讯作者：
Du, Meirong
中科院分区：
文献类型：
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作者：
Huang, Xixi;Liu, Lu;Du, Meirong
常驻记忆T （T- rm）细胞在怀孕期间驻留在子宫可能在平衡母胎耐受性和抗感染免疫方面发挥重要作用。虽然CD8(+)T（RM）和CD8(+)T细胞已被广泛表征，但CD8(+)T(RM) （dT(RM)）细胞的特性仍然不明确。研究方法采用流式细胞术研究dT（RM）细胞的异质性、表型和功能，比较正常妊娠和复发性自然流产（RSA）患者dT（RM）细胞的比例。此外，我们将外周CD8(+)T（CD8(+)pT）细胞与滋养细胞或蜕膜细胞（dsc）在存在或不存在抗tgf - β抗体或tgf - β I型受体抑制剂的情况下共培养，以探索母胎环境对蜕膜CD8(+)T（RM）细胞形成的影响。结果我们发现CD69(+)CD103(+)T（RM）细胞在CD8(+)dT细胞中大量存在，而在具有效应记忆(EM, CD45RA（-)CCR7(-)）表型的CD4(+)dT细胞中不存在。妊娠期妊娠组dT（RM）细胞比例明显高于正常妊娠组。此外，dT（RM）细胞受刺激后，趋化因子受体、t细胞耗竭相关分子的表达增加，产生更多的抗炎因子和效应因子。此外，dsc在CD69(+)CD8(+)pT细胞上产生相当水平的tgf - β并上调CD103的表达，这可以通过阻断tgf - β受体而显著逆转。结论人类妊娠早期蜕膜中存在具有独特性质的T-RM细胞。它们具有增强的产生效应细胞因子和调节分子的能力，这可能在母体-胎儿免疫耐受和积极应对感染的能力之间的平衡中很重要。
Problem Resident memory T (T-RM) cells reside in the uterus during pregnancy may play an important role in balancing maternal-fetal tolerance with anti-infectious immunity. Although CD8(+)T(RM) and decidual CD8(+)T cells have been extensively characterized, the properties of decidual CD8(+)T(RM) (dT(RM)) cells remain poorly defined.Method of study We investigated the heterogeneity, phenotypes, and functions of dT(RM) cells, and compared the proportion of dT(RM) cells between normal pregnancy and recurrent spontaneous abortion (RSA) using flow cytometry. Moreover, we cocultured peripheral CD8(+)T (CD8(+)pT) cells with trophoblast, or decidual stomal cells (DSCs) in the presence or absence of anti-TGF-beta antibody or TGF-beta type I receptor inhibitor to explore the effects of maternal-fetal environment on decidual CD8(+)T(RM) cell formation.Results We found that CD69(+)CD103(+)T(RM) cells were abundant in CD8(+)dT cells but not in CD4(+)dT cells with effector-memory (EM, CD45RA(-)CCR7(-)) phenotypes. The percentage of dT(RM) cells from RSA patients was significantly higher than that from normal pregnancy. Furthermore, dT(RM) cells showed increased expressions of chemokine receptors, T-cell exhaustion-related molecules, and produced more anti-inflammatory cytokines and effector cytokines upon stimulation. Moreover, DSCs produced a considerable level of TGF-beta and upregulated CD103 expression on CD69(+)CD8(+)pT cells, which can be significantly reversed by blocking TGF-beta receptor.Conclusion Our findings demonstrate that T-RM cells with unique properties are present in the decidua during human early pregnancy. They possess an enhanced capacity to produce effector cytokines and regulatory molecules, which might be important in the balance between maternal-fetal immune tolerance and the capacity to aggressively respond to infections.