短期使用雷帕霉素联合调节性T细胞可延长小鼠移植心脏时间但不能抑制受体肿瘤发生

发布时间：2018-05-06 06:11

本文选题：调节性T细胞(Treg) + 心脏移植　；参考：《细胞与分子免疫学杂志》2017年02期

【摘要】：目的研究短期使用雷帕霉素(Rap)联合调节性T细胞(Treg)在诱导同种异体小鼠心脏移植物长期存活,同时探讨此方案对移植受体肿瘤免疫的影响。方法免疫磁珠法分离得到受体小鼠脾脏Treg,经CD3/CD28单克隆抗体磁珠及2000 U/m L重组小鼠白细胞介素2(rm IL-2)体外扩增后,流式细胞术检测纯度;建立小鼠腹腔同种异体心脏移植模型(H-2~b到H-2~d),分为对照组(单纯移植)、Rap组、Rap联合Treg组。Rap组连续14 d经腹腔注射Rap 1 mg/(kg·d),Rap联合Treg组注射相同剂量的Rap,并移植当天经尾静脉过继输注扩增后的1×107个Treg,同时设同基因移植组(H-2~d到H-2~d),每日观察移植心脏搏动并在相应时点进行组织学评价。在受体肿瘤免疫实验中设三组同种异体心脏移植(H-2~b到H-2~d)小鼠,同时经尾静脉过继输注B16-F10细胞(H-2~b)(受体来源),另三组同种异体心脏移植(H-2~d到H-2~b)小鼠经尾静脉过继输注B16-F10细胞(H-2~b)(供体来源),两周后比较肺部肿瘤结节数量。结果对照组移植心脏中位生存时间(MST)为7 d,Rap组为15 d,Rap联合Treg过继输注能够显著延长移植心脏MST至93 d,组织学显示长期存活心脏淋巴细胞浸润及慢性血管病变;对于供体来源肿瘤,对照组未见肿瘤结节,Rap组为(15±8)个,Rap联合Treg组小鼠肺部肿瘤结节为(14±7)个,后2组类似无显著性差异;对于受体来源肿瘤,对照组肿瘤结节为(70±12)个、Rap组为(28±9)个、Rap联合Treg组小鼠肺部肿瘤结节为(146±12)个,与对照组、Rap组相比均显著增加。结论短期使用低剂量Rap联合Treg能够显著延长小鼠移植心脏的存活时间,但仍不能抑制受体肿瘤的发生。
[Abstract]:Objective to study the long-term survival of cardiac allograft induced by rapamycin Rapa combined with regulatory T cell Treg. and to explore the effect of rapamycin Rapa combined with regulatory T cell Tregl on the tumor immunity of transplanted mice. Methods the spleen of the recipient mice was isolated by immunomagnetic bead method and amplified by CD3/CD28 monoclonal antibody magnetic beads and 2000 U / mL recombinant mouse interleukin 2(rm IL-2. The purity was detected by flow cytometry. A model of intraperitoneal allogeneic heart transplantation was established in mice. The mice were divided into two groups: control group (Rap group) combined with Treg group. Rap group was injected intraperitoneally with Rap 1 mg/(kg DX Rap + Treg group for 14 days, and the same dose of Rapa was injected through the tail on the day of transplantation. Pulse adoptive infusion of 1 脳 107 Tregs was performed in the same gene transplantation group. The heart beating was observed daily and the histological evaluation was made at the corresponding time point. Three groups of allogeneic cardiac allografts (H-2B to H-2D) mice were established in the tumor immunological test of the receptor. At the same time, B16-F10 cells were infused via caudal vein to infuse B16-F10 cells (the source of the receptor, the other three groups of allogeneic heart transplantation to H-2B) mice. B16-F10 cells were infused via caudal vein to infuse B16-F10 cells (donor source). The number of pulmonary tumor nodules was compared two weeks later. Results in the control group, the median survival time of the transplanted heart was 7 days, the group of Rap was 15 days old, and the adoptive infusion of Treg could significantly prolong the MST to 93 days. The histology showed that the long-term survival of cardiac lymphocytes infiltration and chronic vascular disease were observed. For donor-derived tumors, the number of lung tumor nodules in the Rap group was 15 卤8 in the control group and 14 卤7 in the Treg group, but there was no significant difference between the latter two groups, while in the receptor-derived tumor group, there was no significant difference between the two groups. The number of lung tumor nodules in the control group was 70 卤12), 28 卤9 in the Rap group and 146 卤12 in the Treg group, which was significantly higher than that in the control group. Conclusion Short-term use of low dose Rap combined with Treg can significantly prolong the survival time of the transplanted heart in mice, but still can not inhibit the occurrence of recipient tumor.
【作者单位】：重庆医科大学附属第一医院肝胆外科;
【基金】：国家自然科学基金(30972789) 重庆市自然科学基金(cstc2013jcyj A10105)
【分类号】：R654.2

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