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首页> 外文期刊>The anatomical record: advances in integrative anatomy and evolutionary biology >Recipient‐Derived Allo‐iTregs Induced by Donor DCs Effectively Inhibit the Proliferation of Donor T Cells and Reduce GVHD
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Recipient‐Derived Allo‐iTregs Induced by Donor DCs Effectively Inhibit the Proliferation of Donor T Cells and Reduce GVHD

机译：供体DCS诱导的受体衍生的Allo-ItRegs有效地抑制供体T细胞的增殖并减少GVHD

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ABSTRACT To compare the potency of recipient‐derived, antigen‐specific regulatory T cells induced by different dendritic cells (DCs; iTregs) and freshly isolated natural regulatory T cells (nTregs) in preventing mouse graft‐versus‐host disease (GVHD) after allogeneic bone marrow transplantation (BMT). CD4 + T cells from recipient BALB/c mice were stimulated with DCs from recipient BALB/c (syn‐DCs), donor B6 (allo‐DCs), and third‐party C3H (third‐party‐DCs) mice to induce different iTregs. In parallel, nTregs were isolated from spleen cells of recipient BALB/c (syn‐nTregs) and donor B6 (allo‐nTregs) mice using magnetic‐activated cell sorting. Mixed lymphocyte reaction (MLR) assays were performed to evaluate the suppressive ability of these various regulatory T cells (Tregs). Both the iTregs and nTregs were transfused to GVHD mice on Days 0, 1, 3, and 5. Body weight, GVHD score, and survival time were monitored. Peripheral Tregs were subsequently examined on Days 7, 14, 21, and 28 after BMT, while chimerism was evaluated on Days 14 and 60. Histopathology of colon, liver, and spleen were also performed. DCs markedly induced CD25 + and Foxp3 + expression on CD4 + T cells. The allo‐DC‐induced Tregs (allo‐iTregs) suppressed the proliferation of alloreactive T cells better than the other iTregs/nTregs in MLR assays ( P 0.05). Meanwhile, transfusion of the allo‐iTregs reduced the severity of GVHD ( P 0.05), increased survival time compared with the GVHD group ( P 0.05), and enhanced the chimerism proportion. On Day 28 after BMT, the allo‐iTregs group had the highest frequency of peripheral Tregs ( P 0.05). Recipient‐derived allo‐iTregs induced by donor DCs included predominant clones that specifically recognized donor antigens. These allo‐iTregs not only prevented GVHD by suppressing the proliferation of donor‐alloreactive T cells, but also promoted engraftment, and prolonged the survival of GVHD mice. Anat Rec, 2018. ? 2018 Wiley Periodicals, Inc. Anat Rec, 302:825–836, 2019. ? 2018 Wiley Periodicals, Inc.
机译：摘要比较不同树突细胞（DCS; ITREGS）和新分离的自然调节T细胞（NTREGS）诱导的受体衍生的抗原特异性调节性T细胞的效力，并在同种异体后预防小鼠移植物与宿主病（GVHD）骨髓移植（BMT）。来自接受者BALB / C小鼠的CD4 + T细胞与来自受体BALB / C（SYN-DCS），供体B6（ALLO-DC）和第三方C3H（第三派对-DCS）小鼠的DCS刺激，以诱导不同的ITREGS 。使用磁性活性细胞分选，从受体BALB / C（SYN-NTREGS）和供体B6（ALLO-NTREGS）小鼠的脾细胞中分离出来的NTREGs。进行混合淋巴细胞反应（MLR）测定以评估这些各种调节T细胞（Tregs）的抑制能力。 ITREGS和NTREGS在0,1,3和5天转发给GVHD小鼠。体重，GVHD评分和存活时间被监测。随后在BMT之后的第7,14,21和28天检查外周Tregs，同时在第14天和第60天评估嵌合体。还进行结肠，肝脏和脾脏的组织病理学。 DCS显着诱导CD25 +和FoxP3 +表达CD4 + T细胞。 Allo-DC诱导的Tregs（Allo-Itregs）抑制了比MLR测定中的其他ITREGS / NTREGS更好地抑制了聚体性T细胞的增殖（P <0.05）。同时，与GVHD组（P <0.05）相比，Allo-ITRegs的输血降低了GVHD（P <0.05）的严重程度，增加了存活时间（P <0.05），并增强了嵌合体比例。在BMT之后的第28天，Allo-Itregs组的外周Tregs的频率最高（P <0.05）。供体DC诱导的受体衍生的Allo-ItRegs包括特异性识别供体抗原的主要克隆。这些Allo-ITRegs不仅通过抑制供体 - 占性T细胞的增殖而预防GVHD，而且促进了植入，延长了GVHD小鼠的存活率。 ANAT REC，2018.？ 2018 Wiley期刊，Inc。Anat Rec，302：825-836,2019。 2018年Wiley期刊，Inc。

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