Human Mesenchymal Stem Cells Are Susceptible to Lysis by CD8+ T Cells and NK Cells
Human Mesenchymal Stem Cells Are Susceptible to Lysis by CD8+ T Cells and NK Cells
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DOI：
10.3727/096368910x564076
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Hoogduijn, Martin J.
中科院分区：
文献类型：
--
作者：
Crop, Meindert J.;Korevaar, Sander S.;Hoogduijn, Martin J.
人们对使用间充质干细胞（MSC）来改善器官移植的结果越来越感兴趣。然而，MSC 的免疫原性尚不清楚，并且对于 MSC 治疗的功效和对供体抗原的潜在致敏作用很重要。我们研究了肾移植环境中自体和同种异体 MSC 对 CD8(+) T 淋巴细胞和 NK 细胞裂解的敏感性。 MSCs来源于人肾供体的脂肪组织，为CD90(+)、CD105(+)、CD166(+)和HLA I类。它们表现出分化能力和免疫抑制能力。通过铕释放测定来测量外周血单核细胞 (PBMC)、FACS 分选的 CD8+ T 细胞和 NK 细胞对 MSC 的裂解作用。同种异体间充质干细胞易被细胞毒性CD8+T细胞和自然杀伤细胞裂解，而自体间充质干细胞仅被自然杀伤细胞裂解。 NK 细胞介导的裂解与 MSC 上 HLA I 类的表达呈负相关。自体 MSC 的裂解不依赖于 FBS 中的 MSC 培养，悬浮液以及粘附在塑料上的 MSC 会被 NK 细胞裂解。移植前的受体 PBMC 不会裂解供体 MSC，但移植后 3、6 和 12 个月分离的 PBMC 显示裂解能力增强。 12个月后，CD8(+) T细胞介导的供体间充质干细胞裂解持续存在，表明没有证据表明对供体间充质干细胞有脱敏作用。当考虑将 MSC 应用于临床时，必须考虑到 MSC 的裂解。我们的结果表明，MSC 的 HLA 背景和 MSC 给药时机对于 MSC 治疗的功效很重要。
There is growing interest in the use of mesenchymal stem cells (MSCs) to improve the outcome of organ transplantation. The immunogenicity of MSCs is, however, unclear and is important for the efficacy of MSC therapy and for potential sensitization against donor antigens. We investigated the susceptibility of autologous and allogeneic MSCs for lysis by CD8(+) T-lymphocytes and NK cells in a kidney transplant setting. MSCs were derived from adipose tissue of human kidney donors and were CD90(+), CD105(+), CD166(+), and HLA class l. They showed differentiation ability and immunosuppressive capacity. Lysis of MSCs by peripheral blood mononuclear cells (PBMCs), FACS-sorted CD8+ T cells, and NK cells was measured by europium release assay. Allogeneic MSCs were susceptible for lysis by cytotoxic CD8(+) T cells and NK cells, while autologous MSCs were lysed by NK cells only. NK cell-mediated lysis was inversely correlated with the expression of HLA class I on MSCs. Lysis of autologous MSCs was not dependent on culturing of MSCs in FBS, and MSCs in suspension as well as adherent to plastic were lysed by NK cells. Pretransplant recipient PBMCs did not lyse donor MSCs, but PBMCs isolated 3, 6, and 12 months after transplantation showed increasing lysing ability. After 12 months, CD8(+) T-cell-mediated lysis of donor MSCs persisted, indicating there was no evidence for desensitization against donor MSCs. Lysis of MSCs is important to take into account when MSCs are considered for clinical application. Our results suggest that the HLA background of MSCs and timing of MSC administration are important for the efficacy of MSC therapy.