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人类妊娠期间的雌激素和孕激素通过激活 T/B 细胞轴来促进体液免疫。

Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating T /B cell axis.

机构信息

Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.

Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Eur J Immunol. 2021 Jan;51(1):167-179. doi: 10.1002/eji.202048658. Epub 2020 Oct 21.

DOI:10.1002/eji.202048658
PMID:33012073
Abstract

Circulating T (cT ) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-γ, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cT 1, cT 2, cT 17, and cT cells, respectively. This CD4 T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cT cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-β-estradiol (E2) directly increased the percentage of different cT subsets. While E2 and progesterone (P4) increased the proportion of differentiated T cells derived from naïve CD4 T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/T cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10 T cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cT and B cell subsets.

摘要

循环 T (cT) 细胞表达 CXCR5、PD-1,并且在激活时表达 ICOS 并释放 IL-21。根据 IFN-γ、IL-4 和 IL-17 的产生以及 FoxP3 的表达,这些细胞也分别被分类为 cT1、cT2、cT17 和 cT 细胞。该 CD4 T 细胞亚群对有效的体液免疫至关重要,妊娠似乎有利于 IgG 的产生。在这里,不仅妊娠增强了乙型肝炎病毒免疫妇女体内抗-HBsAg IgG 的体内产生,而且 cT 细胞的频率与雌二醇水平直接相关。在体外,妊娠相关剂量的 17-β-雌二醇 (E2) 直接增加了不同 cT 亚群的百分比。虽然 E2 和孕酮 (P4) 增加了从幼稚 CD4 T 细胞分化而来的 T 细胞的比例,但只有 E2 增强了这些细胞培养物中 IL-21 的释放。此外,E2 和 P4 分别增加了记忆 B 细胞和浆细胞的比例。在 SEB 激活的 B/T 细胞共培养物中,E2 在 P4 的存在下增加了总 IgG 的产生。最后,在这些激素中,P4 在上调 IL-10 T 细胞的百分比方面更强。总之,我们的研究结果表明,E2 和 P4 通过促进不同 cT 和 B 细胞亚群的扩增来共同参与体液免疫反应。

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