CD8+Treg 介导的对初始 CD4+T 细胞向滤泡辅助性 T 细胞分化的抑制作用。
CD8 Treg-Mediated Suppression of Naive CD4+ T Cell Differentiation into Follicular Helper T Cells.
机构信息
Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, California, USA.
出版信息
Int Arch Allergy Immunol. 2022;183(6):682-692. doi: 10.1159/000521427. Epub 2021 Dec 27.
BACKGROUND
The regulatory CD8+ T (CD8+ Treg) cells play an important role in immune tolerance and have been implicated in several human autoimmune diseases. In this context, follicular helper T (TFH) cells contribute by controlling the antibody production. In mice, CD8+ Treg cells control the number and function of TFH cells however the role of human CD8+ Treg cells on the differentiation of naive CD4+ T cells into TFH cells has not been studied.
OBJECTIVES
Here, we evaluated the ability of human CD183+ CD8+ Treg cells to suppress TFH cell differentiation in vitro.
METHODS
Activated CD183+CCR7+CD45RA-CD8+ Treg and CD183+CD25highICOS+CD8+ Treg cells were sorted and cocultured with naïve CD4+ T cells under TFH differentiation condition. The differentiation of TFH cells was evaluated by flow cytometry.
RESULTS
Our results showed that activated CD183+CD8+ Treg cells upregulated the expression of Forkhead box P3 transcription factor, inducible T-cell co-stimulator (ICOS), and CD25 compared to CD183-CD8+ T cells. The CD183+CD25highICOS+CD8+ Treg cells suppressed TFH cell differentiation and CD4+ T cell proliferation in vitro which was not observed when CD183+CCR7+CD45RA-CD8+ Treg were cocultured with naïve CD4+ T cells under TFH cell differentiation condition.
CONCLUSION
These results suggest that CD25highICOS+CD183+CD8+ Treg cells may regulate autoimmune and inflammatory responses mediated by TFH cells.
背景
调节性 CD8+T（CD8+Treg）细胞在免疫耐受中发挥重要作用，并与多种人类自身免疫性疾病有关。在这种情况下，滤泡辅助 T（TFH）细胞通过控制抗体产生来发挥作用。在小鼠中，CD8+Treg 细胞控制 TFH 细胞的数量和功能，然而，人类 CD8+Treg 细胞对幼稚 CD4+T 细胞分化为 TFH 细胞的作用尚未研究。
目的
本研究评估了人源 CD183+CD8+Treg 细胞体外抑制 TFH 细胞分化的能力。
方法
分选激活的 CD183+CCR7+CD45RA-CD8+Treg 和 CD183+CD25highICOS+CD8+Treg 细胞，并在 TFH 分化条件下与幼稚 CD4+T 细胞共培养。通过流式细胞术评估 TFH 细胞的分化。
结果
我们的结果表明，与 CD183-CD8+T 细胞相比，激活的 CD183+CD8+Treg 细胞上调了叉头框 P3 转录因子、诱导性 T 细胞共刺激因子（ICOS）和 CD25 的表达。CD183+CD25highICOS+CD8+Treg 细胞在体外抑制 TFH 细胞分化和 CD4+T 细胞增殖，而当 CD183+CCR7+CD45RA-CD8+Treg 细胞在 TFH 细胞分化条件下与幼稚 CD4+T 细胞共培养时，未观察到这种现象。
结论
这些结果表明，CD25highICOS+CD183+CD8+Treg 细胞可能调节由 TFH 细胞介导的自身免疫和炎症反应。
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