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脐带来源间充质基质细胞与外周血淋巴细胞混合培养中自然杀伤细胞的激活

Activation of NK Cells in Mixed Cultures of Wharton's Jelly Mesenchymal Stromal Cells and Peripheral Blood Lymphocytes.

作者信息

Svirshchevskaya E V, Poltavtsev A M, Os'mak G Zh, Poltavtseva R A

机构信息

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

Institute of Applied Mechanics, Russian Academy of Sciences, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2018 Jan;164(3):339-343. doi: 10.1007/s10517-018-3985-1. Epub 2018 Jan 8.

Abstract

Mesenchymal stromal cells possess immunosuppressive properties that might be used for the therapy of inflammatory diseases of various geneses. The effects of mesenchymal stromal cells depend on their lifetime in the recipient tissues. During heterologous transplantation, mesenchymal stromal cells are eliminated by NK cells. We studied NK cell formation in mixed cultures of Wharton's jelly mesenchymal stromal cells and peripheral blood lymphocytes from an autologous donor. Lymphocytes were activated by a mitogen or IL-2. The lifetime of mesenchymal stromal cells was estimated by MTT test. Cytotoxic activity and phenotype of NK cells were evaluated by flow cytometry. It was found that activation of NK cells depended on IL-2 and was registered on day 2 of incubation with IL-2. In cultures with mitogen-activated lymphocytes, cytotoxicity was observed after 5-6 days. Cytotoxicity of NK correlated with significant decrease in CD16+ and increase in CD56+ NK and with reduction of mesenchymal stromal cell viability. Thus, the main mechanism of elimination of mesenchymal stromal cells is cytotoxicity of NK cells that depended on IL-2 production.

摘要

间充质基质细胞具有免疫抑制特性,可用于治疗各种病因引起的炎症性疾病。间充质基质细胞的作用取决于它们在受体组织中的存活时间。在异种移植过程中,间充质基质细胞会被自然杀伤(NK)细胞清除。我们研究了来自自体供体的脐带华通氏胶间充质基质细胞与外周血淋巴细胞混合培养物中NK细胞的形成。淋巴细胞通过有丝分裂原或白细胞介素-2(IL-2)激活。通过MTT试验评估间充质基质细胞的存活时间。通过流式细胞术评估NK细胞的细胞毒性活性和表型。结果发现,NK细胞的激活依赖于IL-2,且在与IL-2孵育的第2天即可检测到。在有丝分裂原激活的淋巴细胞培养物中,5-6天后观察到细胞毒性。NK细胞的细胞毒性与CD16+显著降低、CD56+NK细胞增加以及间充质基质细胞活力降低相关。因此,清除间充质基质细胞的主要机制是依赖于IL-2产生的NK细胞的细胞毒性。

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