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骨化三醇对γδ T 细胞和 NK 细胞的免疫激活和抑制作用

英文原题:Immune activating and inhibiting effects of calcitriol on γδ T cells and NK cells.

查看英文原题

Immune activating and inhibiting effects of calcitriol on γδ T cells and NK cells.

PubMed 2022/09/29(内容时间) Immunobiology Q3 · IF 3.1(JCR 2025)

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中文摘要

维生素 D 的免疫调节作用以及维生素 D 缺乏对各种疾病的影响是当前科学研究的一个主题。然而,除了其对骨骼健康的众所周知的影响外,临床研究中很少有数据直接将维生素 D 与硬终点联系起来。

因此,值得注意的是,治疗性抗体利妥昔单抗的有效性与 B 细胞淋巴瘤患者的维生素 D 血清水平相关。利妥昔单抗通过抗体依赖的细胞介导的细胞毒性作用(ADCC)发挥效应,NK 细胞和 γδ T 细胞作为效应细胞。

在此,我们评估并比较了 γδ T 细胞和 NK 细胞在长期体外培养中如何被骨化三醇(维生素 D 的活性代谢物)所修饰。来自健康供者的外周血单个核细胞在体外用唑来膦酸(Zol)和白细胞介素-2(IL-2)的组合刺激,或仅用 IL-2 刺激,并向培养物中加入不同浓度的骨化三醇,培养长达 10 天。

我们的结果证实了早期关于骨化三醇对免疫细胞增殖和干扰素-γ 产生具有免疫抑制作用的报道。在某些条件下,体外与骨化三醇孵育导致 Zol/IL-2 刺激的 γδ T 细胞的利妥昔单抗介导的 ADCC 受到抑制,但 IL-2 刺激的 NK 细胞的细胞毒性活性增加。

本研究直接显示了骨化三醇在细胞水平上的免疫调节活性,并将维生素 D 与 NK 和 γδ T 细胞的抗肿瘤作用联系起来。

展开英文摘要原文

The immune modulatory effects of vitamin D and the impact of vitamin D deficiency on various diseases are a subject of current scientific research.

However, there are few data directly linking vitamin D to hard endpoints in clinical studies, apart from its well-known effects on bone health. It is therefore of interest, that the effectiveness of the therapeutic antibody rituximab is connected to the vitamin D serum level of patients with B cell lymphomas. Rituximab exerts its effect via antibody dependent cell mediated cytotoxicity (ADCC), with NK cells and γδ T cells acting as effector cells.

Here we evaluated and compared how γδ T cells and NK cells are modified by long-term in vitro cultivation with calcitriol, the active metabolite of vitamin D. Peripheral blood mononuclear cells from healthy donors were stimulated in vitro with a combination of zoledronic acid (Zol) and interleukin-2 (IL-2) or with sole IL-2 and different concentrations of calcitriol were added to culture for up to 10 days.

Our results confirmed the earlier reports of immune suppressive effects of calcitriol on immune cell proliferation and interferon-γ production. Under certain conditions, in vitro incubation with calcitriol led to an inhibited rituximab-mediated ADCC of Zol/IL-2 stimulated γδ T cells, but to an increased cytotoxic activity of IL-2 stimulated NK cells.

This study directly shows immune modulatory activity of calcitriol on the cellular level and links vitamin D to anti-tumoral effects of NK and γδ T cells.

论文信息

作者
Bold A、Gross H、Holzmann E、Smetak M、Birkmann J、Bertsch T、Triebel J、Sauer K
单位
Department of Hematology and Medical Oncology, Paracelsus Medical University, Nuremberg, Germany. Electronic address: anna.bold@klinikum-nuernberg.de.Germany
文献类型
非美国政府资助研究
期刊
Immunobiology2022 Nov
原文标识
PubMed 36244091 · DOI 10.1016/j.imbio.2022.152286