[1]	蒋 欣, 乔良伟, 孙 东, 李 明, 房 军, 曲青山. 肾移植患者血清中长链非编码RNA PGM5-AS1表达及调控人肾小球内皮细胞的作用[J]. 中国组织工程研究, 2021, 25(5): 741-745.
[2]	杨 鑫, 金 喆, 冯 旭, 卢 兵. 沈阳市居民对器官、眼组织及遗体捐献的认知及意愿调查[J]. 中国组织工程研究, 2021, 25(5): 779-784.
[3]	王晓勃, 王长安, 韩健乐, 杨青彦, 杨帅平, 杨俊伟. 环孢素转换为他克莫司对稳定期肾移植受者糖代谢和心血管风险的影响[J]. 中国组织工程研究, 2021, 25(14): 2236-2240.
[4]	毛 鑫, 余丽梅, 王 峰. 间充质干细胞在心脏移植免疫耐受诱导中的重要作用[J]. 中国组织工程研究, 2021, 25(13): 2070-2078.
[5]	刘君昌, 高小林, 姜泰茂. CYP3A5基因多态性与肾移植受者他克莫司浓度/剂量的关系及个体化用药[J]. 中国组织工程研究, 2021, 25(11): 1740-1744.
[6]	郭 娟, 郑 珊, 谢 辉, 胡亚会. 肾移植受者422例病原菌感染分析[J]. 中国组织工程研究, 2020, 24(32): 5198-5202.
[7]	蔡秋程，范洪凯，熊日晖，江 艺. 骨髓间充质干细胞对心脏死亡脂肪变供肝移植后肝功能的保护[J]. 中国组织工程研究, 2019, 23(17): 2625-2629.
[8]	杨 进，张美霞，闫 沛，程 乔，李建珍. 肾移植后新发糖尿病危险因素的Meta分析[J]. 中国组织工程研究, 2019, 23(15): 2450-2460.
[9]	蒋珊珊，王 峰，余丽梅. 间充质干细胞免疫调节特性及在器官移植中的应用[J]. 中国组织工程研究, 2019, 23(1): 103-109.
[10]	杨其顺，姜 伟，黄赤兵 . 肾移植后肺部感染分期诊治：可提高肾移植后功能的稳定率[J]. 中国组织工程研究, 2018, 22(8): 1255-1260.
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In decades, inducing transplantation immune tolerance, a more attractive method of inducing graft acceptance through the recipient immune response into accepting the transplanted organ, has been the hot point in region of conquering immunology rejection after allograft or exonograft transplantation^{[1] .} The induction and maintenance of immune tolerance to transplanted tissues constitute an active process involving multiple mechanisms that work cooperatively to prevent graft rejection. These mechanisms are similar to inherent tolerance toward self antigens and have a requirement for active immunoregulation that promotes specific unresponsiveness to donor alloantigens. These mechanisms include T cell depletion through activation-induced cell death, "ignorance" of self antigens and the induction of T cell energy^[2] . While these mechanisms are clearly important in the maintenance of self tolerance, they are by themselves not sufficient, as there is also a need for active suppression of autoreactive T cells by Tregs^[3] . Although initial characterization of these Treg subsets defined their role in the maintenance of tolerance to self, it is now clear that CD4⁺CD25⁺Treg cells play an important role in suppressing immune responses directed against alloantigens expressed on transplanted organs and tissues^{[4 ]} . CD4⁺CD25⁺Treg cells have the potent suppressive effect not only on responder T cells either directly via cell contract or secretion of IL-10 and TGF-β1 or alternatively by influencing the stimulating APC^[5-6] but also on B cell Ig response directly via cell contact^[7] .
However, the total amount of CD4⁺CD25⁺Treg cells has only 5 to 10 percent of CD4⁺ T cells in normal individual peripheral blood, which can only maintain the self immune homeostasis. Obviously, CD4⁺CD25⁺Treg cells, as effective tool cells in inducing transplantation immune tolerance, must be enriched and induced donor antigenic specificity in vitro. Meanwhile, the dose-effect relationship must be taken into account. In this study, we will identify donor antigenic specificity CD4⁺CD25⁺Treg cells induce immune tolerance of allograft kidney transplantation in rats initially. Even to find the dose effect relationship of CD4⁺CD25⁺Treg cells used in vivo.

Organ transplantation is the only effective therapy for patients who suffer from organ end-stage function failure. However, the immunology rejections, either acute rejection or chronic rejection, are always threatening the survival of transplanted organs though there are so many new immunosuppressive drugs have been used in clinical treatment^{[11-12] .} So it is crucial to find a way to prevent and therapy the immune rejection.
It is well known that effect T and naive B lymphocytes play important role in mediate immunity reactions. Naive B lymphocytes mediate humor immunity in major and relate to the chronic rejection mostly. T lymphocytes mediate cell immunity and take part in the progress both acute and chronic rejection. At the same time, the most important host immunological reaction against allo and xeonogenic graft after transplantation is acute cellular rejection, mediated primarily by effect T cells^[13] . So it is certainly an effective strategy to avoid acute rejection directly and chronic rejection indirectly even allow recipients long-term drug free after transplantation by way of inhibit the activation of donor specific reactive T cells selectively.
A role for naturally occurring CD4⁺CD25⁺ Tregs in the development of transplantation tolerance was first indicated by their ability to suppress graft verses host disease in murine models of allogeneic bone marrow transplantation. While transfer of allogeneic CD4⁺CD25^– naive or effector T cells normally leads to graft versus host disease, cotransfer of purified CD4⁺CD25⁺ Tregs along the CD4⁺CD25^– T cells significantly delayed disease onset^[14] . In solid organ and tissue transplantation, cotransfer of CD4⁺CD25⁺ T cells into T cell–deficient mice along naive CD4⁺CD25^– cells can block the ability of the latter cell subset to reject minor or MHC-mismatched allogeneic skin grafts^[15] .  Collectively, these studies indicate that naturally occurring Tregs can play a role in achieving transplantation tolerance.
In vitro, CD4⁺CD25⁺Treg cells can suppress the effect T cells effectively unless the ratio of quantities not less than 1/3. While there are only 3% to 5% of CD4⁺ T cells express the phenotype of CD25⁺ in vivo^{[16] .} As a result, the more CD4⁺CD25⁺Treg cells existed, the more effect T cells were suppressed. So it is a key to get large scale of CD4⁺CD25⁺Treg cells. By way of magnetic cell sorting system (MACS) could we get CD4⁺CD25⁺Treg cells high yield and purity. However, the plan which attempted through promoting disintegration (PMA plus ionomycin) and inducing cytokines (TGF-β1 or IL-10) could not make a satisfied conclusion. Thus, we must build an effect method to expansion CD4⁺CD25⁺Treg cells in future.
As one important immunology characteristics of CD4⁺CD25⁺Treg cells, we must induce CD4⁺CD25⁺Treg cells donor specific phenotype before utilize them inducing immune tolerance in vivo^[17] DCs have been described to play a role in transplantation tolerance and induce regulatory T cells by their tolerogenic properties^{[18-19] .} By way of co-culture donor antigens together CD4⁺CD25⁺Treg cells and iDCs of recipients can we induce CD4⁺CD25⁺Treg cells the phenotype of donor antigenic specificity successfully. At the same time, we also found that donor antigenic specificity CD4⁺CD25⁺Treg cells only induced immune tolerance to the grafts of the donor and the immunology system continues to reject allografts from third parties. This demonstrates that the suppressive effect of CD4⁺CD25⁺Treg cells on effect T cells is antigen specific. Meanwhile, the donor antigenic specificity CD4⁺CD25⁺Treg cells induced by the donor phenotype can only suppress effect T cells the same phenotype as the inducer.
Every thing has two sides, so does CD4⁺CD25⁺Treg cells. From the data we collected from the experiments showing that low quantities of CD4⁺CD25⁺Treg cells can not induce the immune tolerance effectively while the high amount of CD4⁺CD25⁺Treg cells will lead to high risk of infection even malignant tumors. So it is key to definite the right dosage to use CD4⁺CD25⁺Treg cells in inducing immune tolerance in vivo. Meanwhile, the plan of replenishment must be certified if enlarge the period of studies in vivo. That is main project for us to solve replenishment issues in studies followed.
In conclusion, we have demonstrated in this work that donor antigenic specificity CD4⁺CD25⁺Treg cells right dosage may overcome acute rejection effectively and induce immune tolerance in vivo successfully. There are important steps to get plenty of CD4⁺CD25⁺Treg cells and induce them the phenotype of donor antigenic specificity in vitro. Moreover, you must pay more attention to the dose-effect relationship before use donor antigenic specificity CD4⁺CD25⁺Treg cells in vivo.

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