Mesenchymal stem cells together with mycophenolate mofetil inhibit antigen presenting cell and T cell infiltration into allogeneic heart grafts
Mesenchymal stem cells together with mycophenolate mofetil inhibit antigen presenting cell and T cell infiltration into allogeneic heart grafts
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DOI：
10.1016/j.trim.2010.12.002
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发表时间：
2011-04-15
影响因子：
1.5
通讯作者：
Popp, F. C.
中科院分区：
文献类型：
--
作者：
Eggenhofer, E.;Steinmann, J. F.;Popp, F. C.
供体来源的间充质干细胞（MSC）在移植前与霉酚酸酯（MMF）联合注射可诱导大鼠心脏移植模型的长期接受。相反，MSC单独引起加速的移植物排斥。为了更好地理解这些相互矛盾的数据，我们研究了MSC和MMF对心脏移植物和次级淋巴器官中淋巴细胞群的影响，在这个模型中，移植前注射的同种异体MSC具有免疫原性，因为与未用MSC治疗的动物相比，MSC和MSC/MMF治疗的动物的次级淋巴器官中活化的CD 4（+）和CD 8（+）细胞出现得更早。因此，T细胞浸润仅MSC治疗的动物的移植物，迅速引起加速的移植物排斥反应。然而，很少有T细胞或抗原呈递细胞（APC）浸润MSC和MMF治疗的动物移植物。与这一发现相一致，细胞间粘附分子1（ICAM-1）和E-选择素的下调只在MSC/MMF处理的移植物，表明MSC与MMF干扰内皮细胞活化。此外，干扰素-γ（IFN-γ）的存在增强了MSC在体外抑制T细胞增殖的能力。有趣的是，霉酚酸酯不影响血清IFN-γ水平在vivo.Together，我们的数据表明，MSC预活化T细胞，但共同治疗与霉酚酸酯消除这些T细胞，减少移植物内APC和T细胞运输抑制内皮细胞活化，并允许IFN-γ刺激抑制MSC。(C)2010 Elsevier B. V.保留所有权利。
Donor-derived mesenchymal stem cells (MSC) can induce long-term acceptance in a rat heart transplantation model when injected prior to transplantation in combination with mycophenolate mofetil (MMF). In contrast, MSC alone cause accelerated graft rejection. To better understand these conflicting data we studied the effects of MSC and MMF on lymphocyte populations in heart allografts and secondary lymphatic organs.Allogeneic MSC injected prior to transplantation are immunogenic in this model because activated CD4(+) and CD8(+) cells emerged earlier in secondary lymphatic organs of MSC- and MSC/MMF-treated animals, compared to animals not treated with MSC. Consequently T cells infiltrated the grafts of MSC-only treated animals promptly causing accelerated graft rejection. However, few T cells or antigen-presenting cells (APC) infiltrated the grafts of animals treated with MSC and MMF. Consistent with this finding, intercellular adhesion molecule 1 (ICAM-1) and E-selectin was down-regulated exclusively in MSC/MMF-treated grafts, indicating that MSC together with MMF interfere with endothelial activation. Additionally, the presence of interferon-gamma (IFN-gamma) enhanced MSC capabilities to suppress T cell proliferation in vitro. Interestingly, MMF did not influence serum IFN-gamma levels in vivo.Together, our data indicate that MSC pre-activate T cells, but co-treatment with MMF eliminates these T cells, decreases intragraft APC and T cell trafficking by inhibiting endothelial activation, and allows IFN-gamma stimulation of suppressive MSC. (C) 2010 Elsevier B.V. All rights reserved.