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单磷酰脂质A对急性髓系白血病患者树突状细胞成熟的影响。

The Effect of Monophosphoryl Lipid A on Maturation of DCs from Patients with Acute Myeloid Leukaemia.

作者信息

El Husseiny Noha Mohamed, El Fattah Attya Elkak Walaa Abd, El Ansary Mervat Said, El Aziz El Khateeb Engy Mohamed Abd, Mattar Mervat Wagih, El Demerdash Doaa Mohamed

机构信息

Clinical Haematology Unit, Internal Medicine Department, Kasr Al Aini Faculty of Medicine, Cairo University, Cairo.

出版信息

Iran J Immunol. 2017 Mar;14(1):1-12.

PMID:28341814
Abstract

BACKGROUND

Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and generating mature MDDC either alone or in combination with other cytokines.

OBJECTIVE

To compare effects of traditional cytokine cocktail (TNF-α + IL-1β) versus TLR4-agonist monophosphoryl lipid A on the viability, phenotype, cytokine profile and functionality of MDDC.

METHODS

The study included 32 individuals; twenty Acute Myeloid Leukaemia (AML) cases in complete remission and 12 healthy volunteers. They were divided into 3 groups: Group 1: control group: 12 subjects to measure the baseline levels of all markers in the monocytic preparation. Group 2: cytokine cocktail (TNF-α) group, which included 10 AML subjects. Group 3: MPLA group which included 10 AML subjects.

RESULTS

TNF-α group showed higher expression of CD83 than MPLA group indicating higher capacity to induce DC maturation but both were similar in CD86, CCR7 and IL-10 expression. Preparation of dendritic cells from AML cases in remission and loading them with tumor peptides was successful.

CONCLUSION

MPLA effect in DC maturation is comparable with traditional DC maturation cocktail.

摘要

背景

在粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)存在的情况下诱导产生单核细胞来源的树突状细胞(MDDC),并向单核细胞培养物中添加成熟刺激剂以获得适合治疗的成熟树突状细胞(DC)。肿瘤坏死因子-α(TNF-α)是用于激活DC并单独或与其他细胞因子联合产生成熟MDDC的最常用细胞因子。

目的

比较传统细胞因子组合(TNF-α + IL-1β)与Toll样受体4(TLR4)激动剂单磷酰脂质A对MDDC的活力、表型、细胞因子谱和功能的影响。

方法

该研究纳入32名个体;20例完全缓解的急性髓系白血病(AML)患者和12名健康志愿者。他们被分为3组:第1组:对照组:12名受试者,用于测量单核细胞制剂中所有标志物的基线水平。第2组:细胞因子组合(TNF-α)组,包括10名AML受试者。第3组:单磷酰脂质A(MPLA)组,包括10名AML受试者。

结果

TNF-α组CD83表达高于MPLA组,表明其诱导DC成熟的能力更强,但两组在CD86、CC趋化因子受体7(CCR7)和白细胞介素-10(IL-10)表达方面相似。从缓解期的AML病例中制备树突状细胞并加载肿瘤肽是成功的。

结论

MPLA在DC成熟方面的作用与传统的DC成熟组合相当。

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