Donor Lymphocyte Infusion-Mediated Graft-versus-Host Responses in a Preclinical Swine Model of Haploidentical Hematopoietic Cell Transplantation.
Donor Lymphocyte Infusion-Mediated Graft-versus-Host Responses in a Preclinical Swine Model of Haploidentical Hematopoietic Cell Transplantation.
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DOI：
10.1016/j.bbmt.2016.08.011
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Huang CA
中科院分区：
文献类型：
--
作者：
Duran-Struuck R;Matar AJ;Crepeau RL;Teague AGS;Horner BM;Pathiraja V;Spitzer TR;Fishman JA;Bronson RT;Sachs DH;Huang CA
我们以前描述了成功的造血干细胞移植在小型猪的MHC屏障无移植物抗宿主病（GVHD）使用新的降低强度的预处理方案，包括部分瞬时受体T细胞耗竭，胸腺或低剂量全身照射，和环孢素A的短期课程。在这里，我们报告说，这些协议产生的稳定的嵌合动物是强烈抵抗供体白细胞输注（DLI）介导的GVH效应。在临床剂量下耐受嵌合体中的33个总DLIs中，21个未能诱导转化为完全供体造血嵌合体或引起GVHD。我们试图通过几种机制克服这种转化抗性，包括使用致敏供体淋巴细胞，增加DLI剂量，在DLI前通过广泛的受体白细胞分离去除嵌合宿主外周血细胞，以及使用完全不匹配的淋巴细胞。尽管我们进行了尝试，但在我们的模型中对转化的抗性是稳健的，并且当实现转化时，它与大多数动物中的GVHD相关。我们的研究表明，在降低强度的条件下递送未修饰的造血干细胞剂量可以诱导有效的、无GVHD的免疫耐受状态，其对DLI具有强烈抗性。
We previously described successful hematopoietic stem cell engraftment across MHC barriers in miniature swine without graft-versus-host disease (GVHD) using novel reduced-intensity conditioning regimens consisting of partial transient recipient T cell-depletion, thymic or low-dose total body irradiation, and a short course of cyclosporine A. Here we report that stable chimeric animals generated with these protocols are strongly resistant to donor leukocyte infusion (DLI)-mediated GVH effects. Of 33 total DLIs in tolerant chimeras at clinical doses, 21 failed to induce conversion to full donor hematopoietic chimerism or cause GVHD. We attempted to overcome this resistance to conversion through several mechanisms, including using sensitized donor lymphocytes, increasing the DLI dose, removing chimeric host peripheral blood cells through extensive recipient leukapheresis before DLI, and using fully mismatched lymphocytes. Despite our attempts, the resistance to conversion in our model was robust, and when conversion was achieved, it was associated with GVHD in most animals. Our studies suggest that delivery of unmodified hematopoietic stem cell doses under reduced-intensity conditioning can induce a potent, GVHD-free, immune tolerant state that is strongly resistant to DLI.
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DOI：
10.1111/ajt.12560
发表时间：
2014-02
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Leonard DA;Kurtz JM;Mallard C;Albritton A;Duran-Struuck R;Farkash EA;Crepeau R;Matar A;Horner BM;Randolph MA;Sachs DH;Huang CA;Cetrulo CL Jr
通讯作者：
Cetrulo CL Jr
影响因子：
1.8
作者：
Pescovitz, MD;Book, BK;Saalmüller, A
通讯作者：
Saalmüller, A
DOI：
10.1038/nri3226
发表时间：
2012-05-25
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.1
作者：
Frey, Noelle V.;Porter, David L.
通讯作者：
Porter, David L.
影响因子：
20.3
作者：
Mohty, Mohamad;Labopin, Myriam;Rocha, Vanderson
通讯作者：
Rocha, Vanderson