Blood lymphocyte subsets in ATG-treated and allografted rats

A single dose of rabbit antithymocyte globlin (ATG) was given as the sole immunosuppressive therapy in a model of strong MHC barrier rat heart allotransplantation. PVG/c hearts transplanted to Wistar/Kyoto (WKy) rats resulted in long-term surviving (LTS) grafts and cellmediated lympholysis (CML) unresponsiveness in 50% of the animals. The effects of ATG treatment on the peripheral blood lymphocyte subsets were studied by flow cytometry. The absolute T-lymphocyte levels decreased to less than 5% and were normalized after 2 weeks. CD8-positive cells were normalized within 1 week, whereas CD4- and CD5-positive cells remained low. Rats with LTS grafts had low levels of all T-lymphocyte markers, especially the CD4- and CD5-positive cells. Rats rejecting their grafts showed an eightfold increase in levels of CD8- and CD5-positive lymphocytes and a twofold increase in levels of CD4-expressing lymphocytes. It is concluded that ATG treatment causes the immediate elimination of large lymphoid populations as well as long-lasting immunomodulation detectable in peripheral blood.     

Induction therapy including antithymocyte globulin induces marked alterations in T lymphocyte subpopulations after liver transplantation: results of a long-term study

Various immunosuppressive regimens aim to reduce the incidence of acute rejection after liver transplantation. The efficacy of antithymocyte globulin (ATG) induction therapy and short-term effects on the cellular response have been demonstrated in several studies. Nevertheless, information about long-term effects of ATG therapy on cellular responses and frequency of complications is limited. Therefore, we analyzed the effect of ATG administration within a cyclosporine-based induction therapy, including azathioprine and prednisolone, on lymphocyte subsets and activation markers. We divided 35 liver transplant recipients into two groups according to their initial postoperative immunosuppression: a triple group without ( n=15) and a quadruple group with ATG ( n=20). The minimum observation time (flow cytometry analysis, clinical follow-up) was 2 years. Patients treated with ATG had persistently lower percentages of T cells for at least 2 years postoperatively ( P<0.001). The CD4/CD8 ratios were lower in the quadruple group ( P<0.005). The patients in the ATG group revealed a drop in CD25(+) T cells within 2 years ( P<0.05). However, the percentage of CD71(+) and HLA-DR(+) T cells was temporarily higher in patients with ATG treatment ( P<0.05). Patients with ATG treatment showed persistently higher levels of CD8(+)/CD57(+) double positive cells in the late postoperative phase ( P<0.05). In contrast, no differences could be observed between the two groups for major parameters of clinical outcome (acute rejections, severe infections, patient survival). We conclude that ATG therapy induces long-lasting alterations in T-cell subset composition. However, no beneficial clinical effect could be confirmed after liver transplantation.     

青藤碱对肾移植大鼠T细胞亚群的影响

目的：研究青藤碱(SIN)对肾移植大鼠T细胞亚群及肾功能的影响，探讨SIN免疫抑制作用的可能机制。方法：实验分四个组，采用改良式大鼠肾移植术行wistar—SD大鼠单肾移植，观测术后受体鼠的尿量、尿蛋白及血尿素氮(BUN)、血肌酐(Cr)；用免疫组化法测定受体鼠外周血T细胞亚群。结果：与对照组比较SIN可增加受体鼠的尿量而降低其尿蛋白，并与CsA有协同影响；SIN、环孢素A(CsA)能降低受体鼠血BUN及Cr水平，亦见两药的协同作用。SIN能显著降低肾移植大鼠外周血T淋巴细胞，且主要是降低CD4^ T细胞，并与CsA有协同作用；SIN对CD8^ T细胞无明显影响，因而可使CD4^ T／CD8^ T比值下降，并与CsA有协同影响。结论：SIN对大鼠肾移植的急性排斥反应具有一定的抑制作用，并与低剂量CsA产生显著的协同效应。SIN免疫抑制作用机制可能是抑制T细胞亚群，且主要是抑制CD4^ T细胞，使CD4^ T／CD8^ T比值下降。     

免疫调理对脓毒症大鼠中性粒细胞和淋巴细胞亚群的影响

目的研究免疫调理对脓毒症大鼠中性粒细胞和淋巴细胞及其亚群的影响,阐明免疫调理在脓毒症治疗中的作用。方法成功制作SD大鼠盲肠结扎穿孔（CLP）脓毒症模型,被分为假手术组、对照组和实验组,各20只。制作脓毒症模型后分别在3、12、24、48h采血待测。检查外周血涂片、白细胞总数、中性粒细胞、淋巴细胞计数和CD4^＋、CD8^＋T淋巴细胞亚群。结果实验组白细胞计数和中性粒细胞计数比对照组明显降低,而淋巴细胞计数和CD8^＋T淋巴细胞水平比对照组明显升高,P〈0．05。实验组CD8们林巴细胞水平与对照组差异无统计学意义。结论免疫调理可以明显降低脓毒症大鼠白细胞和中性粒细胞,从而减轻炎症反应。免疫调理可以提高脓毒症大鼠淋巴细胞计数和CD4^＋T淋巴细胞,从而改善免疫功能。     

Blood lymphocyte subsets in patients with primary intracranial tumours. Correlation to histological tumour type and anatomical site

Summary The blood lymphocyte population of 118 patients with primary intracranial tumours and healthy volunteers was examined with respect to its size and cellular composition using various rosette tests. The patients had not undergone any surgical intervention or received any treatment with ionizing irradiation or cytotoxic drugs. However, some of them were treated with corticosteroids.It was observed that non-steroid treated patients with oligodendrogliomas, but not patients with other histological types of tumours, had a significantly reduced proportion of active T-lymphocytes forming rosettes with sheep erythrocytes (a type of T-lymphocyte which is activated by foetal calf serum). These patients as well as those with astrocytomas, malignant gliomas (anaplastic astrocytomas and glioblastomas) or miscellaneous tumours (mainly meningiomas) had normal proportions of lymphocytes with receptors for the Fc-part of IgG or C'3 and cells forming rosettes with sheep erythrocytes under more conventional conditions. Patients who were treated with corticosteroids had an increased frequency of lymphocytes with the above Fc-receptor.An association between site of the lesions and cellular composition of the blood lymphocyte population was not detected. The results give further support for the view that the immunological system may be changed in patients with oligodendrogliomas.     

肺移植术后T细胞亚群研究进展

T细胞是肺移植术后免疫应答的主要效应细胞,其细胞亚群水平对肺移植受者机体免疫状态具有重要影响。本文综述CD4^＋ T细胞、CD8^＋ T细胞和调节性T细胞的免疫学机制及其与肺移植术后原发性移植肺功能障碍、排斥反应、免疫耐受和感染等的关系,同时探讨监测肺移植术后T细胞亚群的临床意义。     

膀胱肿瘤患者红细胞免疫功能的变化

目的 探讨膀胱肿瘤患者的红细胞免疫功能状态及与Ｔ淋巴细胞亚群改变的关系。方法 测定３４例膀胱移行细胞癌患者的红细胞Ⅰ型补体受体花环率（Ｃ３ｂＲＲ）、免疫复合物花环率（ＩＣＲ）及４项肿瘤红细胞花环率［直向肿瘤红细胞花环试验（ＤＴＥＲ）、促肿瘤红细胞花环试验（ＥＴＥＲ）、协同肿瘤红细胞花环试验（ＡＴＥＲ）及自然肿瘤红细胞花环试验（ＮＴＥＲ）］,同时用流式细胞仪（ＥＴＥＲ）检测Ｔ细胞亚群,与年龄相近的３     

Thymoglobulin induction in heart transplantation: patient selection and implications for maintenance immunosuppression

Clinical data relating to rabbit antithymocyte globulin (rATG) induction in heart transplantation are far less extensive than for other immunosuppressants, or indeed for rATG in other indications. This was highlighted by the low grade of evidence and the lack of detailed recommendations for prescribing rATG in the International Society for Heart and Lung Transplantation (ISHLT) guidelines. The heart transplant population includes an increasing frequency of patients on mechanical circulatory support (MCS), often with ongoing infection and/or presensitization, who are at high immunological risk but also vulnerable to infectious complications. The number of patients with renal impairment is also growing due to lengthening waiting times, intensifying the need for strategies that minimize calcineurin inhibitor (CNI) toxicity. Additionally, the importance of donor‐specific antibodies (DSA) in predicting graft failure is influencing immunosuppressive regimens. In light of these developments, and in view of the lack of evidence‐based prescribing criteria, experts from Germany, Austria, and Switzerland convened to identify indications for rATG induction in heart transplantation and to develop an algorithm for its use based on patient characteristics.     

Effect of captopril treatment on allograft survival and induction of unresponsiveness in heart-transplanted, ATG-treated rats.

The angiotensin-converting enzyme inhibitor captopril has been suggested to have an immunomodulatory effect both in clinical and experimental studies. To further investigate this possible effect in organ transplantation, captopril was given to inbred rats before transplantation of an allogeneic heart. Captopril was found to prolong graft survival significantly compared to untreated controls. In rats treated with a tolerogenic dose of ATG, additional captopril administration tended to increase the proportion of rats with long-term functioning grafts, but this did not reach statistical significance. It is concluded that captopril displays an immunosuppressive effect that seems to be weak, since no augmentation of ATG-induced transplantation unresponsiveness was seen.     

胸腺五肽对重度创伤失血性休克大鼠复苏中外周血T淋巴细胞亚群的影响

目的观察早期加用胸腺五肽（TP-5）对重度创伤失血性休克复苏大鼠T淋巴细胞亚群的影响。方法 72只健康雄性SD大鼠随机均分为两组,股骨干骨折合并股动脉放血使MAP控制在（35±5）mm Hg 90 min建立重度创伤失血性休克大鼠模型,Ⅰ组选用复方乳酸钠复苏,Ⅱ组采用复方乳酸钠加用TP-5。两组在休克前（T₁）、复苏前（T₂）、休克复苏后12 h（T₃）、24 h（T₄）、48 h（T₅）、72 h（T₆）时各取6只大鼠静脉血以流式细胞仪测量T淋巴细胞亚群含量。结果与T₁时相比,T₂、T₃时两组CD4+含量和CD4+/CD8+比值均有明显降低（P<0.01）,CD8+含量明显升高（P<0.01）,于T₃时达峰值。T₃～T₆时Ⅱ组CD4+含量、CD4+/CD8+比值明显高于Ⅰ组,CD8+含量明显低于Ⅰ组（P<0.05和P<0.01）。结论重度创伤失血性休克大鼠复苏联合应用胸腺五肽较单纯复苏治疗可促进CD4+含量的增加和CD4+/CD8+平衡,从而可能提高机体细胞免疫能力。     

Alterations of naïve and memory B‐cell subsets are associated with risk of rejection and infection in heart recipients

Rejection and infection are relevant causes of mortality in heart recipients. We evaluated the kinetics of the maturation status of B lymphocytes and its relationship with acute cellular rejection and severe infection in heart recipients. We analyzed B‐cell subsets using 4‐color flow cytometry in a prospective follow‐up study of 46 heart recipients. Lymphocyte subsets were evaluated at specific times before and up to 1 year after transplantation. Higher percentages of pretransplant class‐switched memory B cells (CD19+CD27+IgM‐IgD‐ >14%) were associated with a 74% decrease in the risk of severe infection [Cox regression relative hazard (RH) 0.26, 95% confidence interval (CI), 0.07–0.86; P = 0.027]. Patients with higher percentages of naïve B cells at day 7 after transplantation (CD19+CD27‐IgM+IgD+ >58%) had a 91% decrease in the risk of developing acute cellular rejection (RH 0.09; 95% CI, 0.01–0.80; P = 0.02). Patients with infections showed a strong negative correlation between baseline serum B‐cell–activating factor (BAFF) concentration and absolute counts of memory class‐switched B cells (R =   ?0.81, P = 0.01). The evaluation of the immunophenotypic maturation status of B lymphocytes could prove to be a useful marker for identifying patients at risk of developing rejection or infection after heart transplantation.     

风疹病毒先天性感染与新生儿临床表现及T淋巴细胞亚群变化的相关性

目的探讨风疹病毒(RV)先天性感染与出生婴儿临床表现及脐带血T淋巴细胞亚群变化的相关性研究。方法 2009年3月至2010年5月合肥市某医院收集536例新生儿脐带血标本,应用酶联免疫吸附试验(ELISA)检测血清抗-RV-IgM,采用流式细胞术检测抗-RV-IgM阳性脐带血中T淋巴细胞亚群,并追踪新生儿的临床表现。结果新生儿抗-RV-IgM阳性者共有14例,感染率为2.6%,其中有5例患儿出生时出现不同程度的较为典型的临床表现。抗-RV-IgM阳性组与正常对照新生儿组相比:CD3+T淋巴细胞含量降低(P=0.011)、CD4+T淋巴细胞含量降低(P=0.003)、CD8+T淋巴细胞含量较高(P=0.001)、CD4+/CD8+值较低(P=0.005)。其中,抗-RV-IgM阳性有典型的临床表现组CD3+和CD8+T淋巴细胞含量较抗-RV-IgM阳性无典型的临床表现组无显著性差异,而CD4+T淋巴细胞含量降低(P=0.035)、CD4+/CD8+值降低(P=0.008)。结论风疹病毒感染可导致新生儿细胞免疫功能紊乱,而T淋巴细胞亚群变化与新生儿临床表现密切相关。     

皮肌炎活检特点及免疫状态分析

［摘要］ 目的 探讨初发皮肌炎（dermatomyositis,DM）的临床及肌肉活检特征及治疗前后淋巴细胞亚群的影响。方法 回顾性分析27例初发皮肌炎患者临床特征、肌电图及MRI结果;全部患儿均进行右侧大腿股四头肌肌肉活检,记录组织化学（HE、COX、SDH）染色后光镜下观察肌纤维形态、电镜及免疫组化后肌纤维膜特点;观察治疗12周前后PLT、CRP、WBC、免疫球蛋白IgG、IgA、IgM、IgE和CD3+T细胞、CD4+T细胞、CD8+T细胞、CD19+B细胞、CD16+56?NK细胞的变化。结果 治疗12周后CD19+B细胞的比例较基线降低（P<0.05）,CD8、CD3+T细胞比例较基线升高、治疗前后CD16+56?NK细胞较基线变化不明显（P>0.05）,免疫球蛋白IgG、IgM、IgA较基线下降（P<0.05）,27例患儿进行了MRI（右侧大腿）检测,所见双侧臀部、大腿、膝部及双侧小腿上端肌肉、肌肉间隙及皮下脂肪层弥漫性异常信号影,肌电图均显示所测肌肉进行性肌源性损害。25例肌酶明显升高,光镜下均见到个别肌纤维坏死,局部见束周萎缩,未见胞浆内脂滴或糖原空泡,未见破碎红纤维或镶边空泡,肌束膜和肌内膜纤维脂肪组织增生不明显,炎症细胞不明显,COX酶活性正常,Dystrophin提示肌纤维膜呈阳性表达,表达均匀、连续。电镜下肌细胞大小不等,呈现萎缩、变性、坏死改变,其中2例（7.4%）肌酶正常,肌纤维Dystrophin表达可疑减弱（图2）,1例（3.7%）COX染色示少数肌纤维酶活性减低,且SDH/COX见少数蓝纤维（图3）,1例（3.7%）光镜下未见典型束周萎缩（图4）,电镜显示脂滴增多。结论 皮肌炎光镜下均见到个别肌纤维坏死,局部见束周萎缩,MRI 检查能灵敏且无创地显示JDM 患者的肌肉病变。B、T细胞的免疫紊乱参与了皮肌炎发病,同时也可作为皮肌炎治疗疗效判别的指标。     

去细胞异体神经移植后T细胞亚群及细胞内细胞因子的实验研究

目的 为化学去细胞同种异体周围神经移植的临床应用提供进一步的免疫学实验依据.方法 128只BALB/C小鼠分随机分为假手术组、自体神经移植组、新鲜异体神经移植组和化学去细胞异体神经移植组,每组32只.对各实验组分别进行相应的手术.分别在术后3、7、14、28 d将各组8只小鼠脾淋巴细胞进行分离,特异性荧光标记的单克隆抗体作用后,经流式细胞仪检测T淋巴细胞亚群及细胞内细胞因子的水平及其变化趋势. 结果 在各时间点中,化学去细胞神异体经移植组CD3+、CD4+、CD8+、CD25+阳性细胞率以及IL-2、IFN-γ、TNF-α阳性细胞率与假手术组、自体神经移植组相比差异均无统计学意义(P＞0.05).而新鲜异体神经移植组与其他三组比较差异有统计学意义(P＜0.05). 结论 化学去细胞处理的同种异体神经的免疫源性等于或接近于自体神经,明显低于新鲜同种异体神经.     

Antithymocyte globulin for steroid resistant rejection in renal transplant recipients immunosuppressed with triple therapy

Steroid resistant rejection, confirmed histologically, occurred in 35 of 187 consecutive cadaveric renal transplants treated with triple therapy (cyclosporin, azathioprine and prednisolone) in the Oxford Transplant Unit. Twenty-seven of these were treated with a rabbit antithymocyte globulin (ATG) and 19 showed recovery of function. The level of serum creatinine, the renal biopsy appearance and the requirement for dialysis at the start of ATG treatment did not predict which patients would respond to the therapy. One year after transplantation there was no significant difference between the mean plasma creatinine levels of those patients with steroid resistant rejection who had been given ATG and responded (151.6 μmol/l) and those who had responded to steroids alone (165.0 μmol/l). Adverse effects of ATG treatment included a mean fall in white cell count of 62.2% and a mean fall in platelet count of 45.1%. Two of the 27 patients who received ATG died (7.4% mortality). ATG would appear to be an effective treatment of steroid resistant rejection in patients receiving triple therapy immunosuppression, and graft function may subsequently be excellent in those patients who respond to treatment.     

小剂量兔抗人胸腺细胞免疫球蛋白和赛尼哌在肾移植诱导治疗中的应用效果

目的比较小剂量兔抗人胸腺细胞免疫球蛋白（ATG，即复宁）和赛尼哌在肾移植诱导治疗中的应用效果。方法150例尸体肾移植患者分3组，小剂量即复宁组72例（总剂量2．1～3．0mg／kg），赛尼哌组15例（50mg第1、14天各1次），未接受诱导治疗的肾移植受者63例作为对照组。随访6个门，比较3组患者急性排斥反应、DGF发生率和并发肺部感染率。结果即复宁组、赛尼哌组和对照组6个月内发生急性排斥反应分别为4例（5．5％）、1例（6．7％）、10例（15．9％），发生DGF分别为3例（4．2％）．0例、8例（12．7％），并发肺部感染分别为4例（5．1％）、1例（6．7％）、3例（4．8％），发生白细胞减少分别3例（4．2％）、1例（6．7％）、5例（7．9％），发生血小板减少分别2例（2．8％）、1例（6．7％）、5例（7．9％）。结论早期应用小剂最即复宁和赛尼哌是肾移植诱导治疗的合适选择。     

T淋巴细胞亚群检测在肾移植排斥反应与巨细胞病毒感染鉴别诊断中的应用

目的:探讨外周血淋巴细胞亚群的检测在人类同种异体肾移植术后急性排斥反应与巨细胞病毒(CMV)感染的诊断与鉴别诊断中的价值。方法:采用三色流式细胞技术对47例肾移植术后肾功能正常、16例急性排斥反应、11例CMV感染三组患者外周血淋巴细胞中CD3+、CD3+CD4+、CD3+CD8+细胞的百分比进行检测,并计算出CD3+CD4+细胞与CD3+CD8+的比值,分析不同T淋巴细胞亚群在三组患者中的差别,并行t检验。结果:肾功能正常组、急性排斥反应组与CMV感染组外周血淋巴细胞中CD3+细胞的百分比分别为(70.33±10.96)%、(74.46±8.78)%和(74.06±12.94)%,差异无统计学意义;CD3+CD4+细胞的百分比分别为(40.85±9.58)%、(50.85±8.43)%和(28.62±9.40)%,急性排斥反应组及CMV感染组与肾功能正常组相比,差异均有统计学意义(t=3.871;P<0.01。CD3+CD8+淋巴细胞的百分比分别为(27.08±9.40)%、(20.15±5.47)%和(46.32±15.51)%,急性排斥反应组及CMV感染组与肾功能正常组相比,差异均有统计学意义(t=2.787,P<0.01;t=5.346,P<0.01);CD3+CD4+/CD3+CD8+分别为1.78±0.98、2.88±0.76和0.69±0.31,急性排斥反应组及CMV感染组与肾功能正常组相比,差异均有统计学意义(均P<0.01)。结论:检测外周血淋巴细胞亚群的变化,特别是CD3+CD4+/CD3+CD8+比值,对肾移植术后急性排斥反应及CMV感染具有鉴别诊断价值。     

不同病原感染的手足口病患儿外周血T淋巴细胞亚群分析

手足口病是由多种肠道病毒引起的急性传染病,病原以肠道病毒71型（EV7I）及柯萨奇病毒A16型（CoxA16）最为常见。其中EV71型感染发生神经系统严重并发症较多见,而CoxA16型所致临床表现多较轻。我们于2009年初步研究发现手足口病患儿机体免疫细胞改变。