CD4+CD25HiFoxP3+regulatory T cells in long-term cardiac xenotransplantation
CD4+CD25HiFoxP3+regulatory T cells in long-term cardiac xenotransplantation
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DOI：
10.1111/xen.12379
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发表时间：
2018-03-01
影响因子：
3.9
通讯作者：
Mohiuddin, Muhammad M.
中科院分区：
文献类型：
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作者：
Singh, Avneesh K.;Chan, Joshua L.;Mohiuddin, Muhammad M.
背景CD 4 + CD 25（Hi）FoxP 3 + T（Treg）细胞是CD 4 + T细胞中的一个小的亚群，具有免疫调节功能。尽管外周血淋巴细胞（PBL）中Treg细胞的绝对数量很少，但它们在抑制免疫反应方面发挥着重要作用。几项研究表明，Treg细胞的数量，而不是其内在的抑制能力，可能有助于决定移植移植物的长期命运。在这项研究中，我们分析了Treg细胞的长期狒狒收件人谁收到了转基因的心脏异种移植物从猪donors.MethodsHeterotopic心脏异种移植进行狒狒使用的心脏从GTKO.hCD46（n=8）和GTKO.hCD46.TBM（n=5）转基因猪。改良免疫抑制方案包括抗胸腺细胞球蛋白（ATG）、抗CD 20、霉酚酸酯（MMF）、眼镜蛇毒因子（CVF）和共刺激阻断剂（抗CD 154/抗CD 40单克隆抗体）。流式细胞仪分析进行标记的PBL与抗人的CD 4，CD 25，和FoxP 3单克隆抗体（mAb），以分析的Treg细胞的百分比在6只狒狒，存活时间超过2个月（范围：42- 945天）后，接受了猪心脏xenograft.ResultsTotal白细胞计数低，由于在狒狒接受心脏xenograft.hCD46和GTKO.hCD46.hTBM供体猪的免疫抑制。然而，长期异种心脏移植存活狒狒受体的PBL中CD 4 + CD 25（Hi）FoxP 3 Treg细胞的绝对数量增加（15.13 ± 1.50 vs 7.38 ± 2.92; P
BackgroundCD4+CD25(Hi)FoxP3+ T (Treg) cells are a small subset of CD4+ T cells that have been shown to exhibit immunoregulatory function. Although the absolute number of Treg cells in peripheral blood lymphocytes (PBL) is very small, they play an important role in suppressing immune reactivity. Several studies have demonstrated that the number of Treg cells, rather than their intrinsic suppressive capacity, may contribute to determining the long-term fate of transplanted grafts. In this study, we analyzed Treg cells in PBL of long-term baboon recipients who have received genetically modified cardiac xenografts from pig donors.MethodsHeterotopic cardiac xenotransplantation was performed on baboons using hearts obtained from GTKO.hCD46 (n=8) and GTKO.hCD46.TBM (n=5) genetically modified pigs. Modified immunosuppression regimen included antithymocyte globulin (ATG), anti-CD20, mycophenolate mofetil (MMF), cobra venom factor (CVF), and costimulation blockade (anti-CD154/anti-CD40 monoclonal antibody). FACS analysis was performed on PBLs labeled with anti-human CD4, CD25, and FoxP3 monoclonal antibodies (mAb) to analyze the percentage of Treg cells in six baboons that survived longer than 2months (range: 42-945days) after receiving a pig cardiac xenograft.ResultsTotal WBC count was low due to immunosuppression in baboons who received cardiac xenograft from GTKO.hCD46 and GTKO.hCD46.hTBM donor pigs. However, absolute numbers of CD4+CD25(Hi)FoxP3 Treg cells in PBLs of long-term xenograft cardiac xenograft surviving baboon recipients were found to be increased (15.131.50 vs 7.38 +/- 2.92; P