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首页> 外文期刊>International immunopharmacology >PD-1 blockade augments humoral immunity through ICOS-mediated CD4(+) T cell instruction
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PD-1 blockade augments humoral immunity through ICOS-mediated CD4(+) T cell instruction

机译：PD-1通过ICOS介导的CD4（+）T细胞指令增强了体液免疫力

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摘要

Successful applications of PD-1/PD-L1 blockade in multiple cancers highlight the efficacy of immunotherapy mediated by enhancing CD8(+) T cell immunity both in mouse and human. How PD-1 blockade affects humoral immunity remains unclear. Herein we demonstrated that treatment of anti-PD-1 antibody led to the increase in both total IgG and OVA-specific IgG in OVA-immunized mice. However, no effect was observed on Ab affinity maturation. Accumulation of germinal center (GC) and memory B cells was observed in the spleens together with elevated percentages of plasma cells in the spleens and bone marrow. More interestingly, dramatic infiltration of CD4(+) T cells was apparent in GCs after PD-1 blockade with a significant increase in the expression of ICOS. When CD4(+) T cells and B cells from OVA-immunized mice were co-cultured with neutralizing anti-PD-1 Ab in vitro, PD-1 blockade recapitulated the up-regulation of ICOS expression on CD4(+) T cells with the activation of ERK signaling. Suppression of ERK activation not only reduced ICOS expression on CD4(+) T cells but also attenuated IgG production upon PD-1 blockade. Taken together, PD-1 blockade enhances humoral immunity. This process partially relies on more accumulation of CD4(+) T cells in GCs with the up-regulation of ICOS expression and the promotion of B cell terminal differentiation. The regulatory pattern of PD-1 blockade illustrated here provides a new mechanism of how immune checkpoint molecules regulating humoral immune responses.
机译：PD-1 / PD-L1封闭在多种癌症中的成功应用突出了通过在小鼠和人中增强CD8（+）T细胞免疫介导的免疫疗法的疗效。 PD-1封锁如何影响体液免疫仍然不清楚。在本文中，我们证明了抗PD-1抗体的治疗导致OVA-免疫小鼠中总IgG和卵子特异性IgG的增加。但是，在AB亲和力成熟上没有观察到任何效果。在脾脏中观察到生发中心（GC）和记忆B细胞的积聚，以及脾脏和骨髓中血浆细胞的升高百分比。更有意义地，在PD-1阻断后，在GCS中，CD4（+）T细胞的显着渗透在PD-1阻断后显而易见，随着ICO的表达显着增加。当从体外中和抗PD-1 AB的中和抗PD-1 AB共培养CD4（+）T细胞和B细胞，PD-1阻断重新调节CD4（+）T细胞上的ICOS表达的上调ERK信号的激活。抑制ERK激活不仅减少了CD4（+）T细胞上的ICOS表达，而且在PD-1封闭上衰减IgG产生。连合起来，PD-1封闭增强了体液免疫力。该方法部分依赖于GCS中的CD4（+）T细胞的更多累积，其具有ICOS表达的上调和B细胞末端分化的促进。这里所示的PD-1封闭的调节模式提供了一种新的免疫检查点分子如何调节体液免疫反应的新机制。

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  • 来源
    《International immunopharmacology》 |2019年第2019期|共12页
  • 作者

    Zhang Meiyu; Xia Liliang; Yang Yi; Liu Shuai; Ji Ping; Wang Shujun; Chen Yingying; Liu Zhiduo; Zhang Yanyun; Lu Shun; Wang Ying;

  • 作者单位

    Shanghai Jiao Tong Univ Sch Med Dept Immunol &

    Microbiol Shanghai Inst Immunol 280 South;

    Shanghai Jiao Tong Univ Sch Med Dept Immunol &

    Microbiol Shanghai Inst Immunol 280 South;

    Shanghai Jiao Tong Univ Shanghai Chest Hosp Shanghai Peoples R China;

    Shanghai Jiao Tong Univ Sch Med Dept Immunol &

    Microbiol Shanghai Inst Immunol 280 South;

    Shanghai Jiao Tong Univ Sch Med Dept Immunol &

    Microbiol Shanghai Inst Immunol 280 South;

    Shanghai Jiao Tong Univ Sch Med Dept Immunol &

    Microbiol Shanghai Inst Immunol 280 South;

    Shanghai Jiao Tong Univ Sch Med Dept Immunol &

    Microbiol Shanghai Inst Immunol 280 South;

    Shanghai Jiao Tong Univ Sch Med Dept Immunol &

    Microbiol Shanghai Inst Immunol 280 South;

    Shanghai Jiao Tong Univ Sch Med Dept Immunol &

    Microbiol Shanghai Inst Immunol 280 South;

    Shanghai Jiao Tong Univ Shanghai Chest Hosp Shanghai Peoples R China;

    Shanghai Jiao Tong Univ Sch Med Dept Immunol &

    Microbiol Shanghai Inst Immunol 280 South;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

    PD-1 blockade; Humoral immunity; Germinal center; CD4(+) T cells; ICOS; ERK activation;

    机译：PD-1阻断;体液免疫;生发中心;CD4（+）T细胞;ICOS;ERK激活;

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