大鼠CD4^＋CD25^＋调节性T细胞的分离及功能鉴定

目的：研究利用免疫磁珠分选法稳定分离正常大鼠脾脏CD4^＋CD25^＋调节性T细胞的方法。方法：采用免疫磁珠两步法分离大鼠脾组织CD4^＋CD25^＋T细胞。首先采用藻红蛋白（PE）标记的抗CD25抗体和抗PE多功能磁珠试剂盒阳性分选CD25^＋T细胞,再用抗异硫氰酸荧光素（FITC）标记抗体和抗IgG磁珠阳性分选获得CD4^＋CD25^＋T细胞。分离后的细胞经流式细胞仪检测分离纯度,台盼蓝染色检测细胞存活率,体外增殖实验检测其对CD4^＋CD25^-T细胞的免疫抑制作用。结果：两次阳性分选后获得的CD4^＋CD25^＋T细胞纯度为（90.4±1.6）%,细胞存活率为（92.6±2.4）%。体外增殖实验表明,CD4^＋CD25^＋T细胞能明显抑制CD4^＋CD25^-T细胞的增殖（P〈0.01）。结论：采用免疫磁珠法两次阳性分选,可稳定地获得纯度理想并有免疫抑制功能的大鼠CD4^＋CD25^＋T细胞。     

CD4^＋CD25^＋调节性T细胞在维持小鼠肝脏移植自发性免疫耐受状态中的作用

目的 探讨CD4^＋CD25^＋调节性T细胞在维持小鼠肝脏移植免疫耐受状态中的作用。方法 进行小鼠原位肝脏移植,诱导出移植免疫耐受后,向受体注射抗CD25抗体（PC61）以去除CD4^＋CD25^＋T细胞,检测受体内CD4^＋CD25^＋T细胞数量及叉状头／翅膀状螺旋转录因子（Foxp3）的表达以确定CD4^＋CD25^＋T细胞完全被清除,同时观察受体生存时间。结果与同种同系小鼠肝脏移植结果相似,同种异系肝脏移植小鼠的生存时间亦均超过70d。移植免疫耐受诱导后,PC61不同注射方案均能完全去除受体小鼠肝脏、脾脏及血液中的CD4^＋CD25^＋T细胞,且移植肝脏中Foxp3mRNA的表达也明显降低,表明完全去除了CD4^＋CD25。调节性T细胞,但肝脏移植动物生存时间并未受到影响。结论CD4^＋CD25^＋调节性T细胞对于小鼠肝脏移植自发性免疫耐受的维持并非必需。     

近交系大鼠肝移植自发免疫耐受模型的建立及其CD8+CD28-T细胞的作用

目的建立近交系大鼠原位肝移植自发免疫耐受模型,并研究CD8+CD28- T细胞在自发免疫耐受形成中的作用.方法双袖套法建立原位肝移植模型;流式细胞技术检测CD8+CD28- T抑制细胞含量变化;利用补体细胞毒和免疫磁珠方法分离CD8+CD28- T细胞,通过体外混合淋巴细胞反应验证其抑制功能.结果我们成功建立了BN(供体)LEW(受体)原位肝移植自发免疫耐受模型,并发现自发免疫耐受模型大鼠脾脏CD8+CD28- T细胞含量(23.7%±7.2%)显著高于正常大鼠(5.4%±1.5%)和急性排斥组大鼠(6.0%±1.3%),而且,分离纯化后的自发免疫耐受组大鼠脾脏CD8+CD28- T细胞可以抑制混合淋巴细胞反应的增殖,但急性排斥组大鼠脾脏CD8+CD28- T细胞无抑制功能.结论 BN(供体)LEW(受体)原位肝移植模型为自发免疫耐受;脾脏CD8+CD28- T细胞作为一种T抑制细胞,在自发免疫耐受的形成过程中具有重要作用.     

调节性CD4+T细胞在大鼠自发肝移植耐受中的作用

目的 探讨在肝移植的自发耐受模型中，调节性CD4^＋T细胞的免疫抑制作用机制。方法 利用近交系大鼠从Lewis（LEW）到Wistar Furth（WF）的肝移植组合，对移植后不同时期的宿主注射抗CD4的单克隆抗体（Anti-CD4mAb），然后抽血检测丙氨酸氨基转氨酶（ALT）的动态变化；并结合细胞毒性T淋巴细胞（CTL）试验了解宿主脾细胞中T细胞亚群的动态改变。结果 对肝移植自然生存的宿主注射Afiti—CD4mAb后，术后第21天、42天均能够诱导出肝损害（排斥反应），但第56天、100天以上的则未能诱导出来，且该损害能被抗CD8单克隆抗体阻断。另外CTL试验显示宿主的脾细胞中，初始型CTL前体细胞在移植56d后未能检测出来。结论 在自发性肝耐受模型中。宿主术后早期存在由CD4^＋T细胞介导的下调原始效应性T细胞的作用机制。     

来氟米特对狼疮鼠体内CD4^＋CD25^＋Treg细胞的影响

目的：探讨来氟米特（leflunomide）对狼疮小鼠体内CD4^＋CD25^＋调节性T细胞（Treg）及其特异性转录因子Foxp3基因表达水平的影响,分析其发挥免疫调节作用的可能机制。方法：取MRL/Lpr系狼疮小鼠18只随机分成对照组、来氟米特组、醋酸泼尼松组,对其进行药物干预,8周后流式细胞仪检测脾组织CD4^＋CD25^＋Treg数量变化,荧光定量RT-PCR检测各组脾组织Foxp3 mRNA基因表达变化。结果：来氟米特组、醋酸泼尼松组与对照组相比其体内CD4^＋CD25^＋Treg在CD4＋T细胞中所占比例及Foxp3 mRNA的表达均有所增加,差异有统计学意义（P〈0.05）;其中以来氟米特组增加较为显著。结论：来氟米特及醋酸泼尼松均能提高狼疮鼠体内CD4^＋CD25^＋Treg细胞水平及其特异性转录因子Foxp3 mRNA表达水平。推测其缓解SLE发展的机制之一可能是促进了具有抑制自身免疫反应的CD4^＋CD25^＋调节性T细胞增殖所致。     

自发免疫耐受大鼠移植肝内调节性T细胞的生物学特性

目的研究大鼠肝移植后自发免疫耐受的形成与移植肝内CD4~ CD25~ 调节性T细胞(Tr细胞)的关系。方法按供、受者不同将实验分为3组。急性排斥组:DA大鼠为供者,LEW大鼠为受者;自发耐受组:LEW大鼠为供者,DA大鼠为受者;同基因组:供、受者均为DA大鼠。各组均建立大鼠原位肝移植模型。分别在肝移植术后4、7、14、30和90 d时采用密度梯度离心法分离移植肝内淋巴细胞,免疫磁珠分离(MACS)法分选出CD4~ CD25~ Tr细胞;用流式细胞术(FCM)检测细胞纯度,同时分析CD4~ CD25~ Tr细胞比例的变化;体外细胞增殖试验研究CD4~ CD25~ Tr细胞对CD4~ CD25~-T细胞的免疫抑制作用。结果肝移植早期,急性排斥组和自发耐受组移植肝内CD4~ CD25~ Tr细胞比例均明显增加,其中急性排斥组增加更为明显;移植后4 d左右,两组CD4~ CD25~ Tr细胞比例开始下降,急性排斥组的下降幅度较大;移植后30 d,自发耐受组受者的移植肝内CD4~ CD25~ Tr细胞比例达到第2次高峰,约在移植后90 d时下降至正常生理水平。移植后7 d左右,急性排斥组受者均因发生排斥反应而死亡,而自发耐受组受者均存活。此外,CD4~ CD25~ Tr细胞能有效抑制CD4~ CD25~-T细胞的增殖。结论CD4~ CD25~ Tr细胞是一种具有特异免疫调节功能的T细胞亚群,其主动的免疫抑制功能可能是诱导大鼠肝移植自发免疫耐受的机制之一。     

自然成熟型树突状细胞对 CD4+CD25+调节性 T细胞扩增的影响

目的：探讨自然成熟型树突状细胞对CD4^＋CD25^＋调节性T细胞扩增机制。方法：提取DAB／2小鼠脾脏及肝脏细胞,流式细胞仪分离树突状细胞,测定其纯度及表型,加入C3H／HeJ小鼠提取的CD4^＋CD25^＋调节性T细胞混合培养,测定其增殖活性。利用CD4^＋CD25-T细胞测定扩增后的CD4^＋CD25^＋调节性T细胞的免疫抑制活性。结果：成熟型树突状细胞表达高水平的共刺激分子CD40、CD80及CD86,对CD4^＋CD25^＋调节性T细胞扩增效果明显。与新鲜分离的CD4^＋CD25^＋调节性T细胞一样,扩增的CD4^＋CD25^＋调节性T细胞高表达Foxp3,而且均保持了其抑制活性。结论：自然成熟型树突状细胞能扩增CD4^＋CD25^＋调节性T细胞,且扩增后的调节性T细胞保持了其表达活性和抑制活性。     

CD4+CD25+调节性T细胞在肝移植术后腹腔感染中的表达及其作用

目的研究移植后细菌感染CD4^＋ CD25^＋调节性T细胞（Treg）表达的变化。方法以DA大鼠为供体,LEW大鼠为受体,采用改良的Kamada二袖套法建立肝移植模型。术后随机分为3组,G1组术后3d腹腔生理盐水注射;G2组术后3d给予腹腔大肠杆菌注射;G3组术后常规给予免疫抑制药物CsA,3mg/（kg·d）。感染后7d处死动物,每组6个样本,检测血清ALT、TB,并采用流式细胞术检测脾脏Treg的水平,RT-PCR方法检测脾脏Foxp3和肝脏IL-10、TGF-β mRNA的表达。结果G3、G2组Treg表达水平显著升高,分别为：（16.72±0.95）%,（27.4±1.09）%,与G1（9.88±0.98）%比较差异均有统计学意义（P〈0.01）;脾脏Foxp3和肝脏IL-10、TGF-β mRNA表达水平均增加;感染组的肝功虽然较差,与排斥组相比无统计学意义,但从病理切片观察该组肝脏的急性免疫排斥反应减轻,Banff评分有统计学意义。结论大鼠肝移植术后腹腔细菌感染增加了脾脏Treg的表达,促进了免疫抑制作用的发挥,部分减轻了急性排斥反应。     

结肠癌患者外周血 CD4+ CD25+调节性 T细胞检测的临床意义

目的 探讨结肠癌患者外周血CD4^＋CD25^＋调节性T细胞检测的临床意义。方法采用流式细胞技术对51例结肠癌患者和30例健康体检者外周血淋巴细胞CD4及CD25进行了检测。结果（1）结肠癌组CD4^＋CD25^＋细胞明显高于正常对照组（P〈0．05），CD4^＋CD25^＋细胞则显著低于正常对照组（P〈0．05）；（2）结肠癌组手术后患者CD4^＋CD25^＋、CD4^-CD25^＋细胞与手术前相比显著下降（P〈0．05）；（3）结肠癌组淋巴结转移患者CD4^＋CD25^＋细胞明显高于未转移组（P〈0．001）。结论CD4^＋CD25^＋调节性T细胞数可以反映肿瘤患者免疫系统存在抑制状态，且可能与肿瘤的免疫耐受有关，并可反映肿瘤淋巴结转移状况。     

CD4+CD25+调节性T细胞与移植免疫耐受

CD4^＋CD25^＋调节性T细胞是一类具有特殊免疫调节功能的T细胞亚群,它所介导的免疫抑制在移植免疫耐受的诱导和维持中起关键作用。本文对近年来CD4^＋CD25^＋调节性T细胞的作用机制及免疫耐受等方面的研究进行了综述。     

全身照射预处理供体对异基因大鼠肝移植的作用及对受体内CD4~+CD25~+调节性T细胞的影响

目的 探讨全身照射(TBI)预处理诱导大鼠肝移植术后急性排斥反应的发生机制,及CD4~+ CD25~+调节性T细胞的变化在诱导免疫耐受中的作用.方法 以雄性Lewis、DA大鼠为供、受体,随机分为正常对照组、同种肝移植组、自发免疫耐受组、急性排斥反应组.观察各组受体的生存时间及生存率,检测受体术后外周血中ALT、TB含量、Foxp3~+ CD4~+ CD25~+ 调节性T细胞和T细胞亚群上GITR的表达,检测受体术后第14天移植肝的病理变化和受体脾脏CTL杀伤活性.结果 自发免疫耐受组,术后经历短暂排斥反应最终获得免疫耐受并长期存活.急性排斥反应组,在术后第17～21天死亡,与其他组相比,外周血血清中ALT、TB含量明显升高,而Foxp3~+ CD4~+ CD25~+调节性T细胞比例明显降低.TBI预处理大鼠供肝致受体外周血中CD3~+ CD4~+ T细胞上GITR表达降低,CD3~+CD8~+T细胞上GITR表达增加,提高CTL的杀伤活性.结论 通过TBI清除供体大鼠肝移植物中携带的旁路淋巴细胞,致受体外周血中Foxp3~+ CD4~+ CD25~+调节性T细胞表达降低,而使CD3~+ CD8~+T细胞上GITR表达增加,共同诱导大鼠肝移植术后急性排斥反应发生和耐受障碍.     

肝癌患者外周血CD4~+CD25~+调节性T细胞的变化及其意义

目的 探讨应用流式细胞术检测肝癌患者外周血中CD4~+CD25~+调节性T细胞的变化及意义.方法 应用三色免疫荧光流式细胞仪测定37例肝癌患者及30例肝硬化患者外周血T细胞亚群CD4~+CD25~+/CD~+比值.采用酶联免疫吸附试验(ELISA)法检测外周血中转化生长因子β1(TGF-B1)的表达水平.结果 肝癌患者外周血CD4~+CD25~+/CD4~+比值较肝硬化患者显著增高,两者比较差异有统计学意义(P<0.05);肝癌患者外周血中CD4~+CD25~+T细胞水平与肝癌原发肿瘤的大小、TGF-βl呈正相关(P<0.05).结论 肝癌患者外周血中CD4~+CD25~+调节性T细胞增多,对肝癌患者具有免疫抑制作用.     

CD4+CD25+调节性T细胞对小鼠肝脏移植自发性免疫耐受的影响

目的 研究CD4+CD25+调节性T细胞在诱导自发性肝脏免疫耐受中的作用.方法 向受体和供体注射抗CD25抗体(PC61)后进行小鼠原位肝脏移植,观测其生存时间.术后20～30 d切取移植肝脏行HE染色,同时观察CD4+CD25+T细胞对CD4+T细胞和CD8+T细胞功能的影响.结果 去除受体而不是供体小鼠的CD4+CD25+T细胞可以导致肝移植排斥反应.而且,去除CD4+CD25+T细胞使移植物的白细胞浸润明显增多,组织损伤加重.同时,去除CD4+CD25+T细胞导致CD4+T细胞的增殖活性和CD8+T细胞的细胞毒活性明显增强.结论 受体来源的CD4+CD25+调节性T细胞在小鼠肝脏移植免疫耐受诱导中起重要作用.

Abstract：

Objective To examine the contribution of CD4+ CD25+ regulatory T cells to liver transplant tolerance. Methods After injection of anti-CD25 monoclonal antibody (mAb, PC61), mouse orthotopic liver transplantation was performed and survivals were determined. The paraffin-embedded sections of hepatic allografts were cut and stained with hematoxylin and eosin (HE). Furthermore, the effect of CD4+ CD25+ regulatory T cells on proliferative response of CD4+ T cells and cytotoxicity of CD8+ T cells was examined by depleting these regulatory T cells. Results Depletion of these cells in the recipients but not in the donors before liver transplantation caused rejection. Histological analyses of hepatic allografts with PC61 treatment showed extensive leukocyte infiltration and tissue destruction, whereas those in the control group showed minimal changes. Moreover, elimination of CD4+CD25+ T cells resulted in the enhancement of both proliferative response of CD4+ T cells and cytotoxicity of CD8+ T cells against donor-type alloantigen. Conclusions These results suggest that CD4+CD25+ regulatory T cells were important for tolerance induction to hepatic allografts.     

Spontaneous acceptance of mouse kidney allografts is associated with increased Foxp3 expression and differences in the B and T cell compartments

Spontaneous acceptance of organ allografts can identify novel mechanisms of drug-free transplantation tolerance. Spontaneous acceptance occurs in both mouse kidney transplants and rat liver transplants however the early immune processes of mouse kidney acceptance have not been studied. Acceptance of C57BL/6 strain kidney allografts in fully MHC-incompatible B10.BR recipients was compared with rejection (REJ) of heart allografts in the same strain combination. Graft infiltrate and antibody deposition were examined by immunohistochemical staining. Expression of mRNA was measured by quantitative real-time PCR. Apoptosis was examined by TUNEL staining. The majority of kidney allografts were accepted long-term and induced tolerance (TOL) of donor-strain skin grafts, showing that acceptance was not due to immune ignorance. There was an extensive infiltrate of T cells in the TOL kidney that exceeded the level in REJ hearts but subsequently declined. The main differences were deposition of IgG2a antibody in REJ that was absent in TOL, more B cells infiltrating TOL kidneys and a progressive increase in the ratio of CD8:CD4 cells during rejection. There was also significantly greater Foxp3 mRNA expression in TOL. Kidneys from RAG-/- donors were accepted, showing that donor lymphocytes were not necessary for acceptance. Neutralising antibodies to TGF-β administered from day 0 to day 6 did not prevent TOL. On the basis of cytokine expression and apoptosis there was no evidence for immune deviation or deletion as mechanisms of acceptance. In accord with the findings of spontaneous acceptance of liver allografts in rats, the main difference between mouse kidney TOL and heart REJ was in the B cell compartment. The major difference to rat liver allograft acceptance was that apoptosis of infiltrate did not appear to play a role. Instead, increased Foxp3 expression in TOL kidneys implies that regulatory T cells might be important.     

Adoptive transfusion of ex vivo donor alloantigen-stimulated CD4(+)CD25(+) regulatory T cells ameliorates rejection of DA-to-Lewis rat liver transplantation

BACKGROUND: Adoptive transfusion of splenocytes from long-term survivors of a tolerance model of rat orthotopic liver transplantation can induce acceptance of liver allografts in a rejection model preconditioned with donor gamma-irradiation before liver transplantation. Recent studies suggest that the regulatory T cells (Treg cells) in splenocytes from long-term survivors play an important role in the induction of liver graft tolerance, but this observation was made from a rejection model preconditioned with donor gamma-irradiation; little is known about the role of Treg cells in liver graft rejection using a naive rejection model. In this study, we examined the therapeutic potential of CD4(+)CD25(+) Treg cells in a naive rejection model of rat liver transplantation. METHODS: Freshly isolated or ex vivo alloantigen-stimulated CD4(+)CD25(+) Treg cells (1 x 10(6) cells) from naive Lewis RT(1) (LEW) rats were adoptively transferred into another LEW rat on days 1 and 7 after liver transplantation from a Dark Agouti RT1(a) (DA) rat. Recipients were treated with or without oral tacrolimus (FK506) (0.1 mg/kg/day) from days 1 to 7 after transplantation. For ex vivo alloantigen-stimulation, CD4(+)CD25(+) Treg cells from LEW rats were cocultured with mitomycin C-treated DA (donor alloantigen specific) or Brown Norway (BN)(RT1(n), third party) splenocytes for 72 hours. Ex vivo alloantigen-specific CD4(+)CD25(-) T-cell proliferation responses were assessed with fresh and stimulated CD4(+)CD25(+) Treg cells. RESULTS: Freshly isolated, donor alloantigen-stimulated and third-party alloantigen- stimulated CD4(+)CD25(+) Treg cells suppressed antigen-specific CD4(+)CD25(-) T-cell proliferation ex vivo, and adoptive transfusion of these 3 kinds of CD4(+)CD25(+) Treg cells prolonged survival of the liver allografts. The group transfused with the donor alloantigen-stimulated CD4(+)CD25(+) Treg cells had the greatest mean survival among the 3 groups (fresh Treg cells, 21 +/- 2 days, n = 6; third-party alloantigen-stimulated Treg cells, 20 +/- 2 days, n = 6; donor alloantigen-stimulated Treg cells, 30 +/- 2 days, n = 6). When combined with short-term tacrolimus administration, adoptive transfusion of donor antigen-stimulated Treg cells induced the greatest survival time in recipients (greater than 60 days; n = 6). CONCLUSION: Adoptive transfusion of ex vivo donor alloantigen-stimulated CD4(+)CD25(+) Treg cells combined with short-term tacrolimus treatment may represent a new strategy for preventing rejection after liver transplantation.     

Foxp3 regulates human natural CD4+CD25+ regulatory T‐cell‐mediated suppression of xenogeneic response

Sun L, Yi S, O’Connell PJ. Foxp3 regulates human natural CD4+CD25+ regulatory T‐cell‐mediated suppression of xenogeneic response. Xenotransplantation 2010; 17: 121–130. © 2010 John Wiley & Sons A/S. Abstract: Backgrounds: Cellular rejection of xenografts is predominantly mediated by CD4+ T cells. Foxp3 expressing human naturally occurring CD4+CD25+ regulatory T cells (nTregs) have been shown to suppress pathological and physiological immune responses, including the CD4+ T‐cell‐mediated anti‐pig xenogeneic response in vitro. Although Foxp3 is required for nTreg development and their function, the precise role of Foxp3 in regulating Treg suppressive function in xenoimmune response remains to be identified. Methods: In vitro expanded human nTregs were transfected with fluorescein isothiocyanate ‐conjugated Foxp3 small interfering RNA (siRNA) by Lipofectamine 2000. Transfected nTregs were sorted by fluorescence‐activated cell sorting, and then analyzed for Foxp3 gene and protein expression as well as their phenotypic characteristics. Human CD4+CD25? T cells were stimulated with xenogeneic pig peripheral blood mononuclear cell in the presence or absence of nTregs in a coculture or transwell system for evaluation of nTreg suppressive activity. The production of effector cytokines by xenoreactive CD4+CD25? T cells as well as suppressive cytokine by nTregs in their cocultures was examined by ELISA. Results: The siRNA‐mediated Foxp3 knockdown resulted in impaired nTreg anergic state, downregulated expression of nTreg function associated molecules, and reduced production of suppressive cytokines by nTregs, which together leading to impaired nTreg‐mediated suppression of CD4+CD25? T‐cell proliferation and their effector cytokine production in response to xenogeneic stimulation. Conclusions: This study demonstrates that Foxp3 expression is required for human nTregs to maintain their suppressive function in the xenoimmune response.     

CD4+CD25+调节性T细胞、Foxp3 mRNA及可溶性白细胞介素2受体检测在肾移植中的意义

目的 观察肾移植患者外周血中CD4+CD25+调节性T细胞水平及其表面特异性标志物Foxp3和可溶性白细胞介素2受体（sIL-2R）的变化，探讨其在诊断移植肾急性排斥反应中的作用和价值。 方法 选取42例维持性血液透析接受同种异体肾移植治疗的患者及30例健康体检对照者。在患者移植前、移植后1、2、4、8周或发生排斥反应时，以流式细胞仪检测外周血中CD4+CD25+调节性T细胞水平；荧光定量PCR检测Foxp3 mRNA表达；双抗体夹心酶联免疫吸附法（ELISB）检测血浆中sIL-2R水平。 结果 (1)移植后第1、2、4、8周急性排斥反应组CD4+CD25+调节性T细胞、Foxp3 mRNA水平明显低于同期未发生排斥的肾功能稳定组，而sIL-2R水平却显著高于肾功能稳定组。(2)血液透析患者外周血CD4+CD25+调节性T细胞[(9.22±3.53)%]、Foxp3 mRNA[（0.82±0.36）×10-3]及sIL-2R[（856.30±108.24） U/ml]水平与健康对照组[分别为(6.09±1.99)%、(0.50±0.28)×10-3、(247.35±11.24) U/ml]比较，差异均有统计学意义(P < 0.01)。(3)肾移植后随着肾功能的恢复，外周血CD4+CD25+调节性T细胞[(16.53±4.14)%]、Foxp3 mRNA[(4.97±1.94)×10-3]显著升高(P < 0.01)，而sIL-2R[（463.72±31.23）U/ml]水平明显降低(P < 0.01)。(4)当发生急性排斥反应时，CD4+CD25+调节性T细胞[(12.18±2.86)%]、Foxp3 mRNA[(3.15±1.22)×10-3]显著降低(P < 0.01)，而sIL-2R[(748.36±115.41) U/ml]水平明显升高(P < 0.01)，并且这些变化早于Scr的变化。(5)患者移植前后外周血CD4+CD25+调节性T细胞百分率与Foxp3 mRNA水平均呈正相关（分别为r ＝ 0.904、0.932，P < 0.01），但与sIL-2R水平无相关。 结论 外周血CD4+CD25+调节性T细胞、Foxp3 mRNA及sIL-2R水平的测定均可以作为肾移植患者移植后发生急性排斥反应的早期预测指标，并可判断预后。     

CD4+CD25+FOXP3+T细胞在肝癌肝移植肿瘤复发中的作用

目的 探讨肝癌肝移植病人移植前后外周血和肿瘤组织中CD4+CD25+FOXP3+T细胞比例变化及其临床意义.方法 用流式细胞仪检测肝癌肝移植病人和其他肝移植病人术后外周血中CD4+CD25+FOXP3+T细胞的比例,并采用正常人作对照.用免疫组化法检测肝癌病人和非肝癌病人肿瘤组织中FoxP3的表达及CD8+T细胞浸润的比例.观察肝癌肝移植病人术后及肿瘤复发后调节性T细胞的变化及其对肿瘤复发的影响.结果 流式细胞检测显示肝癌肝移植、非肝癌肝移植的病人术后外周血中CD4+CD25+FOXP3+T细胞占CD4+T细胞的比例较正常人明显升高,分别为(10.15±1.00)%、(5.30±1.64)%和(3.20±1.18)%,P<0.05.肝癌肝移植肿瘤复发病人较未复发病人外周血CD4+CD25+FOXP3+T比例明显升高,分别为(15.15±1.50)%和(6.80±1.50)%,P<0.01.免疫组化检测显示肿瘤组织中FOXP3+T细胞增多,CD8+T细胞浸润明显减少.结论 肝癌肝移植肿瘤复发的病人外周血中CD4+CD25+FOXP3+T细胞比例升高.调节性T细胞可能通过减少CD8+T细胞浸润,加速肿瘤复发.