CD28 confers CD4+ T cells with resistance to cyclosporin A and tacrolimus but to different degrees.

IF 2.3 4区 医学 Q3 ALLERGY
Hiroyuki Kawai, Fumiko Yagyu, Aki Terada, Tsukasa Matsunaga, Manabu Inobe
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引用次数: 0

Abstract

Background: Cyclosporin A (CSA) and tacrolimus (TAC) suppress T-cell activation and subsequent proliferation by inhibiting calcineurin. Though they have the same target, CSA and TAC have quite different molecular structures, indicating quantitative and/or qualitative differences in their effects.

Objective: CD28 is a costimulatory molecule that enhances T-cell activation. It has also been shown to attenuate calcineurin inhibitors. In this study, we compared the CD28-mediated resistance of CD4+ T cells to those calcineurin inhibitors and tried to predict CD28's impact on infectious diseases.

Methods: CD4+ T-cell proliferation was induced with anti-CD3 mAb in the presence or absence of anti-CD28 mAb in vitro. CSA or TAC was added at various concentrations, and the half-maximal inhibitory concentration on CD4+ T-cell proliferation was determined. Effects of lipopolysaccharide (LPS) on dendritic cells (DCs) and CD4+ T-cell proliferation were also evaluated in vitro.

Results: Anti-CD28 mAb conferred CD4+ T cells with resistance to both CSA and TAC, and CD28's effect on the latter was approximately twice that on the former. LPS induced expression of CD28 ligands CD80/86 on DCs. The addition of LPS to culture containing DCs seemed to make CD4+ T cells slightly resistant to TAC but not to CSA. However, its effect on the former was very weak under our experimental conditions.

Conclusions: CD28 attenuated TAC more strongly than CSA. Although LPS did not demonstrate strong enough resistance in our in vitro model, TAC might maintain a better antibacterial immune response than CSA in clinical use.

CD28 使 CD4+ T 细胞对环孢素 A 和他克莫司产生抗药性,但程度不同。
背景:环孢素 A(CSA)和他克莫司(TAC)通过抑制钙调蛋白来抑制 T 细胞的活化和随后的增殖。虽然它们的作用靶点相同,但 CSA 和 TAC 的分子结构却截然不同,这表明它们的作用在数量和/或质量上存在差异:目的:CD28 是一种成本刺激分子,可增强 T 细胞的活化。目的:CD28 是一种成本调控分子,能增强 T 细胞的活化,也被证明能减弱钙调蛋白抑制剂的作用。在这项研究中,我们比较了 CD28 介导的 CD4+ T 细胞对这些钙调素抑制剂的抗性,并试图预测 CD28 对传染性疾病的影响:方法:在有或没有抗 CD28 mAb 的情况下,用抗 CD3 mAb 在体外诱导 CD4+ T 细胞增殖。加入不同浓度的 CSA 或 TAC,测定对 CD4+ T 细胞增殖的半数最大抑制浓度。脂多糖(LPS)对树突状细胞(DCs)和CD4+ T细胞增殖的影响也在体外进行了评估:结果:抗 CD28 mAb 使 CD4+ T 细胞对 CSA 和 TAC 都具有抵抗力,CD28 对后者的影响大约是对前者的影响的两倍。LPS 可诱导 DCs 上 CD28 配体 CD80/86 的表达。在含有 DCs 的培养液中加入 LPS 似乎能使 CD4+ T 细胞对 TAC 稍有抵抗力,但对 CSA 却没有。然而,在我们的实验条件下,LPS对前者的影响非常微弱:结论:CD28对TAC的抑制作用比CSA更强。虽然 LPS 在我们的体外模型中没有表现出足够强的抵抗力,但在临床应用中,TAC 可能会比 CSA 保持更好的抗菌免疫反应。
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来源期刊
CiteScore
12.80
自引率
0.00%
发文量
74
审稿时长
>12 weeks
期刊介绍: The Asian Pacific Journal of Allergy and Immunology (APJAI) is an online open access journal with the recent impact factor (2018) 1.747 APJAI published 4 times per annum (March, June, September, December). Four issues constitute one volume. APJAI publishes original research articles of basic science, clinical science and reviews on various aspects of allergy and immunology. This journal is an official journal of and published by the Allergy, Asthma and Immunology Association, Thailand. The scopes include mechanism, pathogenesis, host-pathogen interaction, host-environment interaction, allergic diseases, immune-mediated diseases, epidemiology, diagnosis, treatment and prevention, immunotherapy, and vaccine. All papers are published in English and are refereed to international standards.
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