本文選題：調(diào)節(jié)性T細(xì)胞(Treg) + 心臟移植��； 參考：《細(xì)胞與分子免疫學(xué)雜志》2017年02期

【摘要】：目的研究短期使用雷帕霉素(Rap)聯(lián)合調(diào)節(jié)性T細(xì)胞(Treg)在誘導(dǎo)同種異體小鼠心臟移植物長(zhǎng)期存活,同時(shí)探討此方案對(duì)移植受體腫瘤免疫的影響。方法免疫磁珠法分離得到受體小鼠脾臟Treg,經(jīng)CD3/CD28單克隆抗體磁珠及2000 U/m L重組小鼠白細(xì)胞介素2(rm IL-2)體外擴(kuò)增后,流式細(xì)胞術(shù)檢測(cè)純度;建立小鼠腹腔同種異體心臟移植模型(H-2~b到H-2~d),分為對(duì)照組(單純移植)、Rap組、Rap聯(lián)合Treg組。Rap組連續(xù)14 d經(jīng)腹腔注射Rap 1 mg/(kg·d),Rap聯(lián)合Treg組注射相同劑量的Rap,并移植當(dāng)天經(jīng)尾靜脈過繼輸注擴(kuò)增后的1×107個(gè)Treg,同時(shí)設(shè)同基因移植組(H-2~d到H-2~d),每日觀察移植心臟搏動(dòng)并在相應(yīng)時(shí)點(diǎn)進(jìn)行組織學(xué)評(píng)價(jià)。在受體腫瘤免疫實(shí)驗(yàn)中設(shè)三組同種異體心臟移植(H-2~b到H-2~d)小鼠,同時(shí)經(jīng)尾靜脈過繼輸注B16-F10細(xì)胞(H-2~b)(受體來源),另三組同種異體心臟移植(H-2~d到H-2~b)小鼠經(jīng)尾靜脈過繼輸注B16-F10細(xì)胞(H-2~b)(供體來源),兩周后比較肺部腫瘤結(jié)節(jié)數(shù)量。結(jié)果對(duì)照組移植心臟中位生存時(shí)間(MST)為7 d,Rap組為15 d,Rap聯(lián)合Treg過繼輸注能夠顯著延長(zhǎng)移植心臟MST至93 d,組織學(xué)顯示長(zhǎng)期存活心臟淋巴細(xì)胞浸潤(rùn)及慢性血管病變;對(duì)于供體來源腫瘤,對(duì)照組未見腫瘤結(jié)節(jié),Rap組為(15±8)個(gè),Rap聯(lián)合Treg組小鼠肺部腫瘤結(jié)節(jié)為(14±7)個(gè),后2組類似無顯著性差異;對(duì)于受體來源腫瘤,對(duì)照組腫瘤結(jié)節(jié)為(70±12)個(gè)、Rap組為(28±9)個(gè)、Rap聯(lián)合Treg組小鼠肺部腫瘤結(jié)節(jié)為(146±12)個(gè),與對(duì)照組、Rap組相比均顯著增加。結(jié)論短期使用低劑量Rap聯(lián)合Treg能夠顯著延長(zhǎng)小鼠移植心臟的存活時(shí)間,但仍不能抑制受體腫瘤的發(fā)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 鹵8 in the control group and 14 鹵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 鹵12), 28 鹵9 in the Rap group and 146 鹵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.
【作者單位】： 重慶醫(yī)科大學(xué)附屬第一醫(yī)院肝膽外科;
【基金】：國(guó)家自然科學(xué)基金(30972789) 重慶市自然科學(xué)基金(cstc2013jcyj A10105)
【分類號(hào)】：R654.2

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