红细胞对血液透析患者单个核细胞分泌功能的影响

目的　探讨红细胞 (RBC)与尿毒症病人单个核细胞分泌功能之间的关系。方法　采用细胞培养技术 ,观察正常人RBC、病人自体RBC、绵羊RBC、红细胞膜碎片、鼠抗人淋巴细胞CD2单克隆抗体 (CD2McAb)对血液透析 (血透 )病人单个核细胞 (PBMNC)分泌白细胞介素 2 (IL 2 )、单核细胞(PBMC)分泌肿瘤坏死因子 (TNF)的影响。结果　自体RBC、同种异体RBC以及绵羊RBC、CD2McAb对病人PBMNC、PBMC分泌IL 2、TNF均有增强作用。自体RBC与CD2McAb共同对PBMNC、PBMC分泌IL 2、TNF有促进作用 ,但与单独加入自体RBC或CD2McAb时相比无显著差异。各种红细胞膜碎片、CD4McAb、CD8McAb、小鼠IgG对PBMNC、PBMC分泌IL 2、TNF无影响。结论　RBC对PBMNC、PBMC分泌IL 2、TNF有直接促进作用 ,其机制认为是通过红细胞表面LFA 3与单个核细胞表面CD2受体之间的相互作用所致。     

阻断CD40/CD40L共刺激通路延长大鼠移植肝脏存活时间

T细胞介导的免疫应答在移植排斥反应中起重要作用,共刺激信号在T细胞活化中是不可或缺的,CD40/CD40L可提供共刺激信号.我们利用腺病毒介导CD40Ig融合基因阻断CD40/CD40L通路,探讨其延长移植肝脏存活的机制. 一、材料和方法 1.材料:CD40、白细胞介素(IL)-2、IL-10、干扰素(IFN)-γ酶联免疫吸附试验(ELISA)试剂盒(美国R&D公司),羊抗兔CD40多克隆抗体(Abcam公司).     

长链非编码RNA MEG3靶向下调miR-21对IL-1β诱导的软骨细胞凋亡及炎症反应的影响

目的探究长链非编码RNA母系表达基因3(MEG3)靶向miR-21的作用对白细胞介素1β(IL-1β)诱导的软骨细胞凋亡及炎症反应的影响及其作用机制。方法将细胞分为cTRL组、IL-1β组、LV-MEG3组、miR-21 mimic组和LV-MEG3+mimic组,用IL-1β处理软骨细胞后,加入对应的慢病毒或miRNA mimic处理细胞。RT-PCR检测MEG3、miR-21、基质金属蛋白酶13(MMP-13)、II型胶原蛋白(Collagen II)、聚蛋白聚糖(Aggrecan)基因表达水平,Hoechst检测细胞凋亡,Western blot检测活化半胱天冬酶3(cl-Caspase-3)、cl-Caspase-9、MMP-13、Collagen II、Aggrecan蛋白表达水平和p65、信号传导及转录激活因子3(STAT3)磷酸化比率,试剂盒检测丙二醛(MDA)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、肿瘤坏死因子α(TNF-α)、IL-6、IL-10水平,免疫荧光检测p65的核定位情况。结果与cTRL组比较,IL-1β组miR-21表达,细胞凋亡率,MMP-13基因表达,cl-Caspase-3、cl-Caspase-9、MMP-13蛋白表达,MDA、LDH、TNF-α、IL-6水平,p65和STAT3磷酸化比率,p65核内信号水平升高,MEG3表达,Collagen II、Aggrecan基因和蛋白表达,SOD、GSH、IL-10水平降低;与IL-1β组比较,LV-MEG3组miR-21表达,细胞凋亡率,MMP-13基因表达,cl-Caspase-3、cl-Caspase-9、MMP-13蛋白表达,MDA、LDH、TNF-α、IL-6水平,p65和STAT3磷酸化比率,p65核内信号水平降低,MEG3表达水平,Collagen II、Aggrecan基因和蛋白表达水平,SOD、GSH、IL-10水平升高;miR-21 mimic组各项检测指标的变化与LV-MEG3组相反;与miR-21 mimic组比较,LV-MEG3+mimic组miR-21表达,细胞凋亡率,MMP-13基因表达,MMP-13、cl-Caspase-3、cl-Caspase-9蛋白表达,MDA、LDH、TNF-α、IL-6水平,p65和STAT3磷酸化比率,p65核内信号水平降低,MEG3表达水平,Collagen II、Aggrecan基因和蛋白表达,SOD、GSH、IL-10水平升高。结论MEG3可下调miR-21表达,从而抑制IL-1β诱导的软骨细胞凋亡,缓解炎症反应,其作用机制可能与抑制NF-κB信号通路激活有关。     

不同免疫抑制剂诱导外周血活化T淋巴细胞凋亡的研究

目的探讨各种免疫抑制剂在体外对人外周血淋巴细胞凋亡的诱导作用及其机制。方法从健康人外周血中分离T淋巴细胞，经抗原刺激诱导淋巴细胞活化，将霉酚酸酯（MMF）、环孢素A（CsA）、他克莫司（FK506）、西罗莫司、泼尼松（Pred）、达利珠单抗及硫唑嘌呤（Aza）单独或联合加入静止T淋巴细胞和活化T淋巴细胞中共同培养，3d后，采用共聚焦显微镜、流式细胞仪、DNA片段化电泳分析及逆转录聚合酶链反应基因扩增方法检测淋巴细胞凋亡发生率，酶联免疫吸附试验检测试剂盒测定细胞培养基中自细胞介素2（IL-2）和Fas的表达水平。结果各种免疫抑制剂中，仅Pred能明显促进静止T淋巴细胞凋亡。MMF、Aza及Pred均能促使活化T淋巴细胞发生凋亡（P〈0．05，P〈0．01），而CsA、FK506、西罗莫司及达利珠单抗均抑制活化T淋巴细胞的凋亡（P〈0．01）。两种或三种不同的免疫抑制剂同时加入活化T淋巴细胞的培养基中，其凋亡细胞明显少于对照组（P〈0．01）。FK506和CsA能显著抑制活化T淋巴细胞的Fas和IL-2表达（P〈0．05）。结论MMF、Aza及Pred可能通过Fas／FasL信号通路诱导活化T淋巴细胞的凋亡，而CsA和FK506通过抑制IL-2的产生而阻碍活化T淋巴细胞的凋亡，西罗莫司和达利珠单抗则可能通过阻断IL-2的活化效应而抑制活化T淋巴细胞的凋亡。     

淋巴细胞功能相关抗原1共刺激作用在活动性狼疮肾炎中的作用

目的探讨淋巴细胞功能相关抗原(LFA)1及其信号分子在狼疮肾炎发病机制中的作用。方法 利用免疫沉淀、免疫印迹和RTllPCR技术检测了LFA-1共刺激对19例活动性狼疮肾炎(LN)患者外周血单个核细胞(PBMC)P13-K磷酸化产物、IL-10 mRNA表达的影响。以14例健康献血员作为对照。结果 在CD3 mAb30 ng/ml存在的情况下,LFA-1mAb共刺激明显提高了活动性LN患者PBMC P13-K磷酸化产物表达(P<0.01),伴有IL-10 mRNA表达和蛋白含量增加(P<0.01),抗lFA-1抗体(5μmol/L)加入后明显抑制了P13-K磷酸化产物表达(P<0.01)。在CD3 mAb和LFA-1mAb协同刺激的情况下,P13-K特异抑制剂Wortamannin的加入明显抑制了LN患者PBMCIL-10 mRNA水平和蛋白含量(P<0.01)。结论 LFA-1作为共刺激分子过度活化P13-K可能介导了活动性狼疮肾炎IL-L 10的高效表达。     

IL-12诱导类风湿关节炎和骨关节炎外周血T淋巴细胞STAT4活化状态的比较

目的：比较类风湿关节炎和骨关节炎外周血T淋巴细胞在IL12作用下诱导STAT4酪氨酸磷酸化水平的差异。方法：2007年5月至2009年8月分离提纯20例类风湿关节炎患者[均为女性;年龄28～55岁,平均（45.0±13.0）岁]和20例骨关节炎患者[均为女性;年龄55～75岁,平均（67.0±9.6）岁]的外周血T淋巴细胞,流式细胞仪进行T淋巴细胞纯度鉴定。用50ng/mlIL12分别作用0、10、30、60min后,提取蛋白进行浓度测量,然后进行WesternBlot检测,经蛋白条带灰度扫描,比较IL12作用各时间点类风湿关节炎和骨关节炎T淋巴细胞STAT4酪氨酸磷酸化水平的差异。结果：经过对外周血单核细胞的分离纯化,T细胞纯度达到91%以上;IL12在对骨关节炎和类风湿关节炎T细胞作用30min后达到活化峰值,在各个时间点（10、30、60min）类风湿关节炎外周血T淋巴细胞活化水平均高于骨关节炎。结论：类风湿关节炎外周血T淋巴细胞在IL12作用下STAT4异常活化。     

导入细胞毒性T淋巴细胞相关抗原4融合蛋白基因抑制大鼠移植肝组织中穿孔素mRNA的表达

研究表明,CD28-B7共刺激途径在T淋巴细胞活化中起主要作用,应用细胞毒性T淋巴细胞相关抗原4融合蛋白(CTLA4Ig)分子阻断CD28-B7信号传导通路,导致T淋巴细胞对抗原的特异性免疫无反应性,从而抑制同种异体器官移植排斥反应.     

严重烧伤后小鼠脾脏T淋巴细胞跨膜信号转导的改变与IL－2、IL－10分泌

目的 探索严重烧伤后小鼠脾脏T淋巴细胞功能改变及IL-2、IL-10分泌规律。并从T淋巴细胞活化跨膜信号转导途径寻找导致其改变的原因。方法 检测T淋巴细胞表面抗原受体TCRα/β，辅助刺激分子CD28及参与跨膜信号转导的G蛋白、蛋白酪氨酸激酶(PTK)、蛋白激酶C(PKC)的活性改变，观察伤后不同时相T淋巴细胞增殖转化功能及IL-2、IL—10分泌活性。分析各信号转导分子改变与T淋巴细胞功能活性改变之间的关系。结果 烧伤后T细胞膜表面分子TCRα/β、CD28表达阳性率降低，GTPase活性和膜PTK活性均受抑，但于伤后168h恢复，转膜PKC活性出现先降低后升高的双相改变，且与IL—10水平密切相关。结论 烧伤后T细胞膜表面分子TCRα/β、CD28和跨膜信号转导酶活性的改变是导致伤后IL-2分泌降低、T细胞功能受抑和IL-10分泌先降低后升高双相改变的重要原因。     

转化生长因子-β1差异性诱导CD4+和CD8+T细胞表达转录因子FOXP3的研究

目的 研究CD4+T细胞和CD8+T细胞被转化生长因子-β1(TGF-β1)诱导表达转录因子FOXP3的差异性.方法 给予CD4+T细胞和CD8+T细胞抗T细胞受体(TCR)刺激的同时,加入TGF-β1培养4d后,通过胞内细胞因子染色,分析二者被诱导表达FOXP3的情况.同时通过CFSE标记实验检测被TGF-β1诱导表达FOXP3的淋巴细胞的增殖情况;通过annexin V流式染色检测TGF-β1对于T淋巴细胞凋亡的影响.结果 相对于CD8+T淋巴细胞,TGF-β1主要诱导CD4+T淋巴细胞阳性表达FOXP3[外周血单个核细胞(PBMC):29.66±3.624比7.430±0.643;癌旁组织浸润淋巴细胞(NIL):31.74±2.612比8.637±1.146].被TGF-β1诱导表达FOXP3的淋巴细胞增殖活跃(94.39±1.179),受到活化刺激后依旧能够有效分泌干扰素-γ(IFN-γ)效应细胞因子(39.58±1.611).TGF-β1能够有效降低CD8+T淋巴细胞活化后的细胞凋亡率(25.39±2.158比9.320±0.3219).结论 与肝癌患者FOXP3表达阳性的淋巴细胞＞95％(97.15±0.3807,n=10)集中在CD4+T淋巴细胞的结果一致,TGF-β1优先选择性诱导CD4+T细胞表达FOXP3.与天然Treg(调节性T细胞)低增殖活性和低细胞因子分泌活性不同,被TGF β1阳性诱导表达FOXP3的T细胞依旧具有活跃的细胞增殖和分泌IFN γ效应细胞因子的功能.CD8+T淋巴细胞相对于CD4+T淋巴细胞,更易发生活化后细胞凋亡,而TGF-β1能够有效降低这种细胞凋亡率.     

CTLA-4与移植免疫研究新进展

CTLA-4是一种负性共刺激信号，属于免疫球蛋白超家族，表达在活化的T细胞、B细胞和APC8表面，与B7分子结合后可阻止IL-2的分泌、抑制IL-2R基因表达、促进TGF-β分泌，从而抑制T细胞的增殖和活化。CTLA-4-Ig是一种融合蛋白，可与B7结合阻断CD28／B7正性共刺激信号通路，诱导供者抗原特异性耐受。因此，CTLA-4成为防治移植排斥反应研究的热点之一。     

人-鼠抗CD4嵌合抗体的生物学效应研究

目的 探讨人－鼠抗ＣＤ４嵌合抗体的生物学效应,方法 观察ＣＤ４人－鼠嵌合抗体和鼠源性单抗对ＣＤ３,植物血凝素（ＰＨＡ）,白细胞－２（ＩＬ－２）及同种异体细胞诱导增殖的影响,以及介导的抗体依赖性细胞介导的细胞毒性（ＡＤＣＣ）作用。结果 提示ＣＤ４嵌合抗体和鼠源性ＣＤ４抗体对以上几种诱导剂诱导的增殖均有抑制作用,且抗体剂量越大,抑制作用越强。     

体外诱导骨肉瘤特异性细胞毒T淋巴细胞的实验研究

研究诱导骨肉瘤特异性细胞毒Ｔ淋巴细胞,及其体内外的抗肿瘤作用。方法：通过生化方法提取纯化骨肉瘤相关抗原,并与低剂量ＩＬ２、ＣＤ３ＭｃＡｂ协同刺激骨肉瘤致敏的淋巴细胞诱导产生ＯＳＳ－ＣＴＬ。结果：ＯＳＳ－ＣＴＬ表型特征为以ＣＤ３＋ＣＤ８＋ＣＴＬ为主的异质细胞群;对ＯＳＡＡ相关的肉瘤细胞显示高亲和杀伤活性。     

结合半乳糖基抗CD3单抗的肿瘤浸润淋巴细胞对自体肝癌细胞杀伤的形态学研究

目的　获取与半乳糖基抗CD3 单抗结合的肿瘤浸润淋巴细胞 (McAb TIL)杀伤自体肝癌细胞的形态学证据 ,并进行杀伤机制探讨。方法　制备McAb TIL ,将其与H2 2 小鼠肝癌细胞共同孵育 ,于不同时间在倒置显微镜和透射电镜下观察。结果　McAb TIL呈增殖活化状态 ,与靶细胞共同孵育 0 .5h即可导致靶细胞严重损伤。杀伤靶细胞后的McAb TIL结构清晰、完整。凋亡与坏死形态学改变可共存于同一个被杀伤靶细胞。结论　偶联了大量半乳糖基的抗CD3 单抗仍具有很强的肿瘤浸润淋巴细胞 (TIL)活化作用。McAb TIL通过多种杀伤机制杀伤自体肝癌细胞 ,杀伤力极强 ,具有连续杀伤靶细胞的能力。     

Impaired antigen-presenting cell function contributes to T-cell hyporesponsiveness in stable lung transplant recipients

BACKGROUND: Peripheral blood mononuclear cells (PBMC) of stable renal or cardiac transplant recipients were previously shown to respond to allogeneic cells but not to soluble protein antigens. The aim of the present study was to assess the T-cell and antigen-presenting cell (APC) functions of stable lung transplant (LT) recipients. METHODS: We obtained PBMC from 38 stable LT recipients. PBMC from healthy volunteers served as controls. PBMC were stimulated with either anti-CD3 monoclonal antibody, allogeneic PBMC, or tetanus toxoid (TT). T-cell activation was assessed by determination of interleukin (IL)-2 levels in culture supernatants; in some experiments, interferon-y levels were also determined. Patients' APC function was tested in a mixed leukocyte reaction using patients' PBMC as stimulators. The expression of class II MHC, B7.2, and CD40 molecules on patients' APC was determined by flow cytometry, and their production of IL-10 and IL-12 at the basal state and upon CD40 ligation was also measured. RESULTS: Patients' T cells produced normal amounts of IL-2 in response to anti-CD3 monoclonal antibody and allogeneic PBMC. In contrast, the response of memory T cells to TT was severely blunted both in terms of IL-2 and interferon-y production. Patients' PBMC were poor stimulators in mixed leukocyte reaction, and class II MHC expression on patients' monocytes was significantly reduced. Patients' APC presented a modest but significant increase in basal IL-10 production and produced significantly less IL-12 upon CD40 ligation than control APC. CONCLUSIONS: T cells from stable LT recipients respond normally to stimuli that do not depend on autologous APC. The major impairment in the T-cell response to TT is caused by APC dysfunction, which involves decreased class II MHC expression and deficient IL-12 synthesis.     

An Unexpected Counter‐Regulatory Role of IL‐10 in B‐Lymphocyte‐Mediated Transplantation Tolerance

Monoclonal antibody against the CD45RB protein induces stable transplantation tolerance to multiple types of allograft. We have previously established that this tolerance protocol relies on the regulatory function of B lymphocytes for its effect. B lymphocytes have also been reported to participate in immune regulation in several other settings. In most of these systems, the regulatory function of B lymphocytes depends on the production of IL‐10. Therefore, we investigated the role of IL‐10 in the anti‐CD45RB model of B‐cell‐mediated transplantation tolerance. Surprisingly, using antibody‐mediated neutralization of IL‐10, IL‐10‐deficient recipients and adoptive transfer of IL‐10‐deficient B lymphocytes, we found that IL‐10 actually counter‐regulates tolerance induced by anti‐CD45RB. Furthermore, neutralization of IL‐10 reduced the development of chronic allograft vasculopathy compared to anti‐CD45RB alone and reduced the production of graft reactive alloantibodies. These data suggest that the participation of regulatory B lymphocytes in transplantation tolerance may be distinct from how they operate in other systems. Identifying the specific B lymphocytes that mediate transplantation tolerance and defining their mechanism of action may yield new insights into the complex cellular network through which antigen‐specific tolerance is established and maintained.     

Enhanced Immunoprotective Effects by Anti‐IL‐17 Antibody Translates to Improved Skeletal Parameters Under Estrogen Deficiency Compared With Anti‐RANKL and Anti‐TNF‐α Antibodies

Activated T cell has a key role in the interaction between bone and immune system. T cells produce proinflammatory cytokines, including receptor activator of NF‐κB ligand (RANKL), tumor necrosis factor α (TNF‐α), and interleukin 17 (IL‐17), all of which augment osteoclastogenesis. RANKL and TNF‐α are targeted by inhibitors such as denosumab, a human monoclonal RANKL antibody, and infliximab, which neutralizes TNF‐α. IL‐17 is also an important mediator of bone loss, and an antibody against IL‐17 is undergoing phase II clinical trial for rheumatoid arthritis. Although there are a few studies showing suppression of Th17 cell differentiation and induction of regulatory T cells (Tregs) by infliximab, the effect of denosumab remains poorly understood. In this study, we investigated the effects of anti‐TNF‐α, anti‐RANKL, or anti‐IL‐17 antibody administration to estrogen‐deficient mice on CD4⁺ T‐cell proliferation, CD28 loss, Th17/Treg balance and B lymphopoesis, and finally, the translation of these immunomodulatory effects on skeletal parameters. Adult Balb/c mice were treated with anti‐RANKL/‐TNF‐α/‐IL‐17 subcutaneously, twice a week, postovariectomy (Ovx) for 4 weeks. Animals were then autopsied; bone marrow cells were collected for FACS and RNA analysis and serum collected for ELISA. Bones were dissected for static and dynamic histomorphometry studies. We observed that although anti‐RANKL and anti‐TNF‐α therapies had no effect on Ovx‐induced CD4⁺ T‐cell proliferation and B lymphopoesis, anti‐IL‐17 effectively suppressed both events with concomitant reversal of CD28 loss. Anti‐IL‐17 antibody reduced proinflammatory cytokine production and induced Tregs. All three antibodies restored trabecular microarchitecture with comparable efficacy; however, cortical bone parameters, bone biomechanical properties, and histomorphometry were best preserved by anti‐IL‐17 antibody, likely attributable to its inhibitory effect on osteoblast apoptosis and increased number of bone lining cells and Wnt10b expression. Based on the superior immunoprotective effects of anti‐IL‐17, which appears to translate to a better skeletal preservation, we propose beginning clinical trials using a humanized antibody against IL‐17 for treatment of postmenopausal osteoporosis. © 2014 American Society for Bone and Mineral Research.     

Differential cytokine expression and regulation of human anti-pig xenogeneic responses by modified porcine dendritic cells

Abstract: Background: Porcine dendritic cells (DC) are likely to be pivotal cells in the initiation of stimulatory and potential tolerogenic responses to xenoantigens, however, there are limited studies characterizing these antigen presenting cells. Methods: Porcine PBMC (CD172a⁺) were cultured with GM‐CSF and IL‐4 and phenotype and functional capabilities assessed. Lipopolysaccharide (LPS), IL‐10, and IL‐3 were added to the GM‐CSF/IL‐4 DC cultures to determine phenotypic and functional changes. Quantitative real‐time polymerase chain reaction (PCR) for key cytokines was performed and the modified porcine DC were further assessed by primary mixed lymphocyte reaction to determine the effect of LPS, IL‐10, and IL‐3 on stimulatory capability. Results: Porcine PBMC (CD172⁺) cultured with GM‐CSF and IL‐4 produced cells with DC morphology, which were major histocompatability complex (MHC) class II⁺, CD14^?/lo, and CD1a^lo. Addition of IL‐10 or IL‐3 to GM‐CSF/IL‐4 DC cultures produced cells with lower levels of MHC class II and higher levels of antigen uptake consistent with less mature DC. Quantitative real‐time PCR of DC showed the addition of IL‐10 induced an increase in IL‐10 mRNA, no detectable IL‐12, and reduced IL‐6 mRNA. The addition of IL‐3 to DC cultures decreased IL‐12, IL‐6 and tumor necrosis factor (TNF), with no change in IL‐10 mRNA. GM‐CSF/IL‐4 DC induced strong human lymphocyte proliferation, compared with significantly reduced stimulatory capacity induced by IL‐10 and IL‐3 treated DC cultures. Conclusions: The profound effect on differential DC cytokine profile and reduced human anti‐pig responses has important therapeutic implications in xenotransplantation. The mechanism of altered regulation warrants further investigation.     

Development of a Microarray for Studying Porcine Cytokine Production in Blood Mononuclear Cells and Intestinal Biopsies

A microarray for demonstration of a limited number of porcine cytokines was initiated. Polymerase chain reaction (PCR) products were synthesized for four house‐keeping genes, cyclophilin, β‐actin, hypoxanthine phosphoribosyltransferase (HPRT) and glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), and the following cytokines: interleukin (IL)‐1β, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12 p35, IL‐12 p40, IL‐18, interferon (IFN)‐α, IFN‐β, IFN‐γ, tumour necrosis factor (TNF)‐α, macrophage inhibition factor (MIF) and granulocyte/macrophage colony‐stimulating factor (GM‐CSF). Cytokine production was induced by incubation of porcine peripheral blood mononuclear cells (PBMC) with Concanavalin A (ConA) or oligodeoxynucleotide (ODN) 2216. RNA was isolated after 6 or 24 h from stimulated cells or unstimulated control cells and from intestinal biopsies. Cytokine expression was analysed using a 3‐DNA Array 350^TM labelling kit from Genisphere. Data were normalized using external control genes and analysed with the genepix pro 5.0 software. All the cytokines could be induced in PBMC and expressed on the array and the cytokines IL‐6 and IFN‐α were also analysed at protein level. All but one cytokine were expressed in samples from intestinal biopsies. Densitometric analyses of PCR products of the house‐keeping genes were performed to validate the results from the microarray. Thus, this microarray will enable analyses of the cytokine profile during local and systemic infections in the pig.     

鼠抗人CD3、CD4单克隆抗体治疗肾移植后急性排斥反应的疗效观察

目的　探讨鼠抗人单克隆抗体预防及治疗尸肾移植后排斥反应的效果。方法　总结和分析了６２ 例肾移植后应用鼠抗人单克隆抗体ＷｕＴ３ 、ＷｕＴ４ 预防及治疗排斥反应的效果、单克隆抗体治疗期间血清游离单克隆抗体水平与受者抗鼠抗体的产生等情况。结果　该抗体对急性排斥反应的总体治愈率为７６ ．１ ％ , 对耐激素的难治性排斥反应的逆转率达６０ ．７ ％ ; ＣＤ３ 和ＣＤ４ 的抑制效应与血清游离单克隆抗体浓度密切相关; 首次应用单克隆抗体治疗时, 抗体的产生与否及量的多少并不影响疗效; 在单克隆抗体治疗的过程中, ＣＤ４／ＣＤ８ 下降明显者, 排斥逆转的可能性大; 停止治疗后Ｔ 淋巴细胞亚群未恢复正常水平者, 感染率明显上升。结论　ＷｕＴ３ 、ＷｕＴ４ 对肾移植后急性排斥反应, 包括耐激素急性排斥反应具有较为满意的治疗效果。