肺癌患者外周血CD4^＋CD25^＋调节性T细胞的检测及意义

目的研究肺癌患者外周血CD4^＋CD25^＋调节性T细胞（Treg）的比例变化,探讨其与肺癌的临床分期、病理类型及组织学分化程度的相关性。方法采用流式细胞术检测78例肺癌患者（肺癌组）和30例健康对照者（健康对照组）外周血CD4^＋CD25^＋Treg占CD4^＋T细胞的比例。结果肺癌组外周血CD4^＋CD25^＋Treg占CD4’T细胞的比例为（21．07±5．26）％,与健康对照组（10．04±2．75）％比较,差异有统计学意义（P〈0．05）;Ⅲ、Ⅳ期肺癌患者外周血CD4^＋CD25^＋Treg比例分别为（22．46±4．35）％、（24．35±6．20）％,显著高于Ⅰ期＋Ⅱ期肺癌患者（12．89±3．19）％及健康对照组（10．04±2．75）％相比,差异有统计学意义（P〈0．05）;鳞癌、腺癌、小细胞肺癌患者外周血CD4^＋CD25^＋Treg比例分别为（20．75±4．85）％、（21．52±5．26）％、（19．20±6．41）％,与健康对照组比较,差异均有统计学意义（P〈0．05）,但不同病理类型的肺癌患者间外周血CD4^＋CD25^＋Treg比较,差异无统计学意义（P〉0．05）;高分化、中分化、低分化肺癌患者外周血CD4^＋CD25^＋Treg比例分别为（20．36±3．12）％、（21．11±4．67）％、（21．30±5．75）％,显著高于对照组（P〈0．05）,但不同分化程度的各肺癌者间比较,差异无统计学意义（P〉0．05）。结论肺癌患者外周血CD4^＋CD25^＋Treg水平明显升高,且与肺癌的进展密切相关,但与病理类型、组织学分化程度无关。     

急性白血病患者CD4+CD25+FoxP3+调节性T细胞、IL-17和IL-23的表达及临床意义

目的观察急性白血病(AL)患者外周血中CD4+CD25+FoxP3+调节性T细胞比例、血清白细胞介素(IL)17和IL-23的表达及其临床意义。方法用流式细胞术测定25例AL患者[急性髓系白血病(AML)15例,急性淋巴细胞白血病(ALL)10例]和10例健康体检者(对照组)外周血中CD4+CD25+FoxP3+调节性T细胞比例,ELISA法测定血清中IL-17和IL-23的表达,分析其间的相关性。结果 AML患者组CD4+CD25+FoxP3+调节性T细胞比例显著高于对照组[(6.52±3.25)vs.(3.58±1.02)](P<0.05);AML和ALL组血清IL-17水平显著高于对照组[(7.21±2.00),(7.47±1.63)vs.(4.52±1.62)](P<0.05)。AL患者血清IL-17和IL-23水平显著正相关(P<0.05)。结论 CD4+CD25+Foxp3+调节性T细胞和IL-17细胞在AML的免疫功能抑制中可能有重要作用,而IL-17细胞在ALL的免疫功能抑制中可能产生作用。     

Immunosuppression based on mycophenolate mofetil in stable liver transplanted patients

AIM: To analyze our results with mycophenolate mofetil (MMF) in stable liver transplantation (LT) patients presenting with adverse events (AE) related to prolonged use of calcineurin inhibitors (CNI). METHODS: Conversion to MMF was performed in 56 out of 323 LT patients from 91-02: 24 (43%) were converted to MMF in monotherapy and 32 (57%) to MMF+low doses of CNI. The indication for conversion was chronic renal insufficiency (CRI) in all patients. The mean time between AE and conversion was 38.7+/-30 months (r: 2-101 m). Post-conversion follow-up was 39+/-20 months (r: 3-72 m). RESULTS: The calculated creatinine clearance (Crauckoft), improved significantly in all patients. In those converted to MMF, improvement was seen during the first 18 months for urea and during the first 6 months for creatinine. In patients converted to MMF+CNI, improvement was maintained throughout the conversion period for both urea and creatinine. Eleven (19.6%) patients underwent acute rejection (2 severe episodes in the MMF group and 1 death). Hypertension was present in 31 patients but only improved in 4 (7%). Dyslipemia was found in 12 and improved in 4 (7%). DM was present in 14 and improved in 1 (2%). CONCLUSIONS: Conversion to MMF in monotherapy is useful in stable LT patients with CRI due to CNI, although this result is offset by more severe rejections. Therefore, for AE secondary to CNI, we propose an early conversion to MMF+low doses of CNI as a first step. If liver function remains stable and AEs persist or progress, conversion to MMF in monotherapy is recommended, as a second step, with close monitoring of the patient.     

Clinical trial: switch to combined mycophenolate mofetil and minimal dose calcineurin inhibitor in stable liver transplant patients--assessment of renal and allograft function, cardiovascular risk factors and immune monitoring

BACKGROUND: Calcineurin inhibitor (CNI)-related nephrotoxicity significantly contributes to chronic renal failure after liver transplantation. METHODS: In this prospective study, liver transplantation patients with renal dysfunction were randomized either to receive mycophenolate mofetil (MMF) followed by stepwise reduction of CNI with defined minimal CNI-trough levels (MMF group), or to continue their maintenance CNI dose (control group). Immune monitoring was performed in a subgroup of the patients. RESULTS: In the MMF group (n = 50), renal function assessed by serum creatinine improved >10% in 62% of patients, was stable in 36% and deteriorated >10% in 2% after 12 months compared with baseline values. Mean serum creatinine levels (+/- s.d.) significantly decreased from 1.90 +/- 0.44 mg/dL to 1.61 +/- 0.39 mg/dL and the corresponding calculated glomerular filtration rate significantly increased from 38.8 +/- 9.6 mL/min/1.73 m(2) to 47.0 +/- 11.8 mL/min/1.73 m(2) over a 12-month follow-up period. Blood pressure and levels of liver enzymes significantly decreased. In the control group (n = 25), there were no significant changes with respect to the investigated parameters. The MMF group had significantly lower numbers of circulating cytotoxic T cells compared with the controls; whereas regulatory T cells significantly increased. CONCLUSION: Combined MMF and minimal dose CNI therapy after liver transplantation is nephroprotective and may promote allograft tolerance.     

Targeting CD4+CD25+FoxP3+ regulatory T-cells for the augmentation of cancer immunotherapy

CD4+CD25+FoxP3+ T-regulatory (Treg) cells are vital to the maintenance of peripheral self tolerance and are implicated in tolerance to foreign antigens. Increasing evidence shows that Treg cells may also play an important role in immune evasion mechanisms employed by cancer. Treg cells are actively recruited and induced by tumors to block innate and adaptive immune priming, effector function and memory response, which can inhibit the efficacy of therapeutic cancer vaccines. As such, modulation of Treg cell function in cancer has been studied using various approaches, with encouraging preclinical and clinical findings. However, controlled and effective modulation of Treg cell function for cancer therapeutics will be contingent on a better understanding of the molecular basis of Treg cell interaction with tumor cells and ensuing immunosuppressive mechanisms.     

薏苡仁酯对高龄恶性肿瘤患者Treg细胞的影响

目的探讨薏苡仁酯(coixenolide)对高龄恶性肿瘤患者外周血调节性T细胞(Treg)的作用。方法检测30例80岁以上老年恶性肿瘤患者(肿瘤组)薏苡仁酯治疗前后外周血Treg占总CD4+T细胞比例和血IL-2mRNA变化。结果与30例健康老年人(对照组)进行比较。结果肿瘤组外周Treg占总CD4+T细胞比例、血IL-2mRNA水平均明显高于对照组(P<0.01)。肿瘤组外周血Treg比例与血IL-2mRNA水平呈正相关(r=0.921,P<0.01)。肿瘤组在薏苡仁酯治疗2个周期后,外周血Treg、IL-2mRNA水平较治疗前明显下降(P<0.01)。结论薏苡仁酯可能通过下调IL-2分泌和Treg数目解除免疫抑制而发挥抗肿瘤作用。     

CD4~+CD25~+调节性T细胞在不同肝脏肿瘤中的表达及意义

目的:研究CD4+CD25+调节性T细胞(Treg)在不同肝脏肿瘤中的分布特点,评价其在肿瘤发生和发展中的作用.方法:根据病理诊断结果将80例肝脏肿瘤分为肝局灶性结节状增生(FNH)组10例、不典型腺瘤样增生(AAH)组10例以及原发性肝癌(HCC)组60例.另选取10例正常肝组织(肝血管瘤边缘肝组织)石蜡包埋标本为对照组.采用双重酶标免疫组化染色的方法测定不同肝脏肿瘤切片中Treg细胞的表达状况.对比分析Treg细胞在FNH、AAH和HCC各组中的表达特点,并进一步分析在HCC组中Treg细胞表达的影响因素.结果:对照组及FNH组中均未发现Treg细胞的表达.AAH组、HCC组中有Treg细胞的表达,且HCC组较AAH组增多(P＜0.01).在癌旁组织中已有Treg 细胞浸润,但较肝癌组织中Treg细胞数量少(P＜0.01).肝癌组织中不同患者性别、年龄、术前AFP水平的Treg细胞数量差异无统计学意义,而在不同肿瘤大小、肿瘤包膜是否完整及术前HBV-DNA水平是否升高中Treg细胞数量差异有统计学意义(P＜0.05或P＜0.01).结论:Treg细胞的表达与肿瘤的发生和发展有关,在肿瘤免疫中起负调节作用.     

Stimulation-dependent induction of CD154 on a subset of CD4+ FoxP3+ T-regulatory cells

CD40-ligand/CD154 is predominantly expressed on activated CD4 T cells and plays a central role in regulating CD4 T-cell-dependent responses. To define the relative abilities of CD4 T-cell functional subsets in the induction of CD154--specifically FoxP3- effector, versus FoxP3+ regulatory, CD4 T cells--multiple CD4 T cell preparations were isolated from B6 and B6.FoxP3-GFP mice and stimulated in vitro to examine the kinetics of stimulation-dependent CD154 expression. CD154 was induced in 40-60% of total CD4 T cells in various cell preparations. However, despite similar kinetics of CD154-induced expression, the average percentage of CD154 expression among CD4+ FoxP3+ T regulatory (Treg) cells was only about 4-9%. Such differential, stimulation-dependent CD154 induction by total CD4+ T cells versus CD4+ FoxP3+ Treg cells was consistent, despite multiple stimulation conditions utilizing a variety of cell preparations of different composition. Similar induction of CD154 occurred irrespective of whether the CD4+ FoxP3+ Treg cells were first sorted to 98% purity and stimulated in vitro alone, or stimulated as non-purified cells in the presence of CD4+ FoxP3- T effector cells, suggesting that CD154 induction by CD4+ FoxP3+ Treg cells is regulated by cell-intrinsic mechanisms. Differential CD154 induction may be a key factor in determining the distinguishable functions of FoxP3- T-effector, versus FoxP3+ Treg, CD4+ T cells.     

CNI induced Th17/Treg imbalance and susceptibility to renal dysfunction in renal transplantation

Calcineurin inhibitors (CNI) prevent graft rejection by blocking interleukin-2 (IL-2), which was required for development and function of Foxp3⁺CD4⁺CD25⁺ regulatory T cells (Treg). Recently, IL-2 was reported to play a part in the inhibition of Th17 cells. The renal transplantation recipient who used CNI regularly might have Th17/Treg imbalance with increased Th17 cells and decreased Treg cells, which would cause renal dysfunction even rejection. To assess the effect of CNI on Th17 cells and Treg cells, we included 123 renal transplantation recipients (101 in a stable stage and 22 with renal dysfunction) and 27 healthy volunteers. Among all the recipients, 103 recipients used CNI and 20 recipients used sirolimus without CNI. The recipients who used CNI were further classified into four groups according to the blood levels of CNI: Of all these subjects, Th17 and Treg frequencies in the peripheral blood were analyzed by flow cytometry (FCM). Serums IL-17, IL-23, IL-6, IFN-r, and TGF-β were analyzed by ELISA. The results demonstrated that the transplantation recipient treated by CNI revealed an obvious increase in peripheral Th17 frequencies and a significant decrease in Treg frequencies when compared with the sirolimus group and healthy people (P < 0.05). Even more, the transplantation recipient with renal dysfunction had the highest level of Th17 cells (P < 0.05) while the lowest Treg cells compared with stable recipient and healthy control, with increased serums IL-6 and IL-17. Our results indicated that CNI was associated with Th17/Treg imbalance in peripheral blood, which supported the followed generation of renal dysfunction after transplantation.     

Reductive alteration of the regulatory function of the CD4(+)CD25(+) T cell fraction in silicosis patients

Causal links have been documented between silica and rheumatoid arthritis, lupus erythematosus, systemic sclerosis and glomerulonephritis. Two different effects of silica have been suggested, an enhanced inflammatory response in the pulmonary region (e.g. activation of alveolar macrophages) and dysregulation of autoimmunity. Based on our previous reports showing in vitro activation of peripheral T cells by silica and reduced regulatory function of the peripheral CD4(+)CD25(+) fraction in which FoxP(3)+ regulatory T cells (Treg) are located, reconstitution of the CD4(+)CD25(+) fraction in silicosis patients (SILs) was investigated. Since T cells in peripheral CD4(+)CD25(+) and CD4(+)CD25(-) (effector T cells; Teff) fractions from SILs showed higher expression of pd-1 (a marker gene for T cell activation) in comparison to that of healthy donors (HDs), chronic T cell activation was considered to have occurred in SILs. In this study, a higher expression of the CD95/Fas molecule in Treg was recorded from silicosis patients (SILs) compared to healthy donors (HDs), and excess loss of FoxP3(+) Treg in freshly isolated peripheral blood mononuclear cells (PBMCs) from SILs relative to HDs was demonstrated when these cells were cultured with silica ex vivo, whereas CD25(+) cells were not reduced due to contamination of activated Teff in the CD4(+)CD25(+) fraction. The activation of both Teff and Treg results in reconstitution of the peripheral CD4(+)CD25(+) fraction, loss of Treg and contamination of activated Teff, resulting in reduction of the number and function of Treg. These results contribute to our understanding of the development of autoimmune diseases found in SILs.     

外用他克莫司对寻常型银屑病患者CD4^＋CD25^＋调节性T细胞的影响

目的 探讨外用他克莫司对寻常型银屑病患者外周血CD4^＋CD25^＋调节性T细胞（CD4^＋CD25^＋Treg）的影响.方法 给予48例寻常型银屑病患者他克莫司软膏,每日2次外用,用药8周.治疗前和治疗后,用流式细胞仪检测患者外周血CD4^＋CD25^＋调节性T细胞的表达水平,并对患者进行PASI评分.结果 治疗8周后,总有效率为91.5%.治疗前,银屑病进行期、静止期患者及正常人外周血CD4^＋CD25^＋Treg与CD4＋淋巴细胞的百分比为（2.64±0.86）%、（3.98±0.96）%、（8.46±1.54）%,三者比较,差异均有极显著性（P＜0.01）;治疗后,进行期和静止期患者外周CD4^＋CD25^＋Treg与CD4＋淋巴细胞的百分比较治疗前均有明显升高（P＜0.01）,但仍低于正常人,三者比较,差异均有极显著性（P＜0.01）.结论 寻常型银屑病存在CD4^＋CD25^＋调节性T细胞异常,他克莫司可通过上调CD4^＋CD25^＋调节性T细胞来治疗寻常型银屑病.     

Introduction of MMF in conjunction with stepwise reduction of calcineurin inhibitor in stable liver transplant patients with renal dysfunction

Mycophenolat mofetil (MMF) is a new imunosuppressant without nephrotoxic adverse effects. The aim of this study was to evaluate feasibility and effect of MMF introduction in conjunction with stepwise reduction of calcineurin inhibitors (CNI) in stable liver transplant patients with chronic CNI-induced renal dysfunction (RDF). In the MMF-group (n=27) but not in the controls (n=16), mean serum level of creatinine fell from a baseline of 227.4+/-67.9 micromol/l to 159.2+/-48.2 micromol/l (P<0,001), while mean urea level declined significantly from a baseline of 18.5+/-8.7 mmol/l to 11.4+/-4.2 mmol/l 6 months after initiation of MMF. Additionally, systolic and diastolic blood pressure values improved. In 52% of patients, dose reduction (n=11) or withdrawal (n=3) of MMF was necessary due to gastrointestinal or hematologic adverse effects. But also in patients on low dose MMF, there was a significant improvement of renal function without increased immunological risk.     

调节性T淋巴细胞在HCV感染者病程不同阶段的表达

目的探讨CD4+CD25+调节性T细胞(Treg)在HCV感染者病程不同阶段的表达及其意义。方法收集非活动性HCV感染33例(A组)、活动性HCV感染32例(B组)、慢性丙型肝炎56例(C组)、HCV相关性肝硬化47例(D组)、HCV相关性肝癌45例(E组)和健康对照者60例(F组),采用流式细胞术检测外周血CD4+T细胞中CD4+CD25+Treg的表达频率,并进行统计学分析。结果 B、C、D、E组外周血CD4+T细胞中CD4+CD25+Treg的表达频率均明显高于F组(P<0.01)。组间比较,A组患者外周血的CD4+CD25+Treg细胞表达频率明显低于B、C、D、E组(P<0.01),D、E组表达频率明显高于B、C组(P<0.01)。结论 HCV感染导致CD4+CD25+Treg细胞的增殖与活化,使机体对其的免疫清除不完全,从而促进HCV感染者疾病的进展和肝癌的发生。     

Resveratrol induces the suppression of tumor-derived CD4+CD25+ regulatory T cells

CD4+CD25+ regulatory T cells (Treg cells) are negative regulator of the immune system and main obstacles to cancer immunotherapy in tumor-bearing hosts. Resveratrol is a natural product found in grapes with both immunomodulatory and anticancer effects, which can be controlled by Treg cells. Therefore, to determine whether resveratrol performs these actions via Treg cells, we investigated changes in Treg cell population and immunomodulatory cytokines in EG7 tumor-bearing C57BL/6 mice. In the present study, CD4+CD25+ cell population among CD4+ cells was inhibited ex vivo by resveratrol treatment in a dose-dependent manner. FoxP3+ expressing cells among CD4+CD25+ population were significantly reduced after resveratrol treatment ex vivo in intracellular FACS analysis. Single intraperitoneal administration of 4 mg/kg resveratrol suppressed the CD4+CD25+ cell population among CD4+ cells and downregulated secretion of TGF-beta, an immunosuppressive cytokine, measured from the spleens of tumor-bearing mice. Furthermore, resveratrol enhanced IFN-gamma expression in CD8+ T cells both ex vivo and in vivo,leading to immune stimulation. Taken together, these results suggest that resveratrol has a suppressive role on CD4+CD25+ cell population and makes peritumoral microenvironment unfavorable to tumor in tumor-bearing mice. Thus, resveratrol can be considered as possible adjuvant material for vaccination-based cancer therapy.     

新辅助化疗前和化疗后乳腺癌组织中CD44+/CD24-/乙醛脱氧酶1细胞表型的变化及意义

目的 探究新辅助化疗(NAC)前后乳腺癌组织中CD44+/CD24-/乙醛脱氢酶1(ALDH1)+细胞表型的比例变化及其临床意义.方法 选取153例经空芯针穿刺活检明确病理诊断的乳腺浸润性导管癌患者为研究对象,临床Ⅱa～Ⅲb期,取NAC前后乳腺癌灶组织,应用免疫组织化学(IHC)单染及双染技术检测并比较化疗前后乳腺癌组织中ALDH1+、CD44+CD24-表型以及两者重叠表达的情况,并分析其与乳腺癌临床病理特征及化疗效果的关系.结果 NAC前患者乳腺癌组织中AL-DH1+/CD44+/CD24-表型的比例为7.2％,化疗后ALDH1+/CD44+/CD24-表型比例为22.9％,两者差异有统计学意义(χ2=14.737,P<0.001);化疗前CD44+/CD24-/ALDH1+表型的表达与肿瘤大小(χ2=5.889,P=0.015)、脉管癌栓(χ2=15.223,P<0.001)、HER-2(χ2=4.036,P=0.045)有显著相关性.NAC前表型为ALDH1+/CD44+/CD24-的患者NAC后有效率(81.8％)明显高于非ALDH1+/CD44+/CD24-表型的患者(45.4％)(χ2=5.748,P=0.017).结论 NAC可促进AL-DH1+/CD44+/CD24-的表型比例升高,ALDH1+/CD44+/CD24-的表型与化疗有效率相关,ALDH1+/CD44+/CD24-表型有可能可以作为预测乳腺癌患者NAC疗效的临床指标.     

Reduced function of CD4+25+ regulatory T cell fraction in silicosis patients

The quality and quantity of CD4+25+ regulatory T cells (Treg) in silicosis patients (SIL) were examined and compared with results from healthy donors (HD) because SIL often develop autoimmune diseases along with pulmonary disorders. Peripheral blood mononuclear cells from 57 SIL and 50 HD were analyzed for Treg. Treg frequency and clinical parameters were subjected to a factor analysis. Treg and CD4+25- T cells (Tneg) from five HD and five SIL, sorted by flow-cytometer, were used for functional assays of Treg, the expression pattern of Treg specific genes (FoxP3, GITR and CTLA-4) and activation-related genes (CD122 and CD123). Although the actual frequency of Treg did not differ between SIL and HD, the age-corrected level was reduced in SIL. The factor analysis showed that Treg frequency was positively associated with the serum level of IL-2. The inhibitory effect of Treg on Tneg activation was decreased when the Treg:Tneg ratio was 1:1/4 to 1/2. In addition, Treg dominancy of FoxP3 and CTLA-4 expression and Tneg dominancy of CD132 expression found in HD were lost in SIL. These results indicated that the Treg fraction in SIL may be substituted with chronically activated T cells due to recurrent exposure to silica, resulting in a reduction in the frequency and function of Treg. Since the reduction of Treg may precede the clinical manifestation, as silicosis may be a pre-clinical status for autoimmune diseases, control of Treg function using cell and/or gene therapy may be a good way to manage autoimmune disease.     

广州地区健康学龄前儿童CD4+CD25nt/hiCD127loTreg细胞在外周血中的表达

目的 初步确定广州地区健康学龄前儿童外周血CD4+CD25nt/hiCD127lo/Treg细胞的表达,建立学龄前儿童CD4+CD25nt/hiCD127loTreg细胞的正常参考范围,为临床研究相关疾病提供参考依据.方法 收集150名3～6岁体检健康的学龄前儿童外周血,采用多色免疫荧光素标记和流式细胞术检测外周血中CD4+CD25nt/hiCD127loTreg细胞的表达.结果 健康学龄前儿童CD4+CD25nt/hiCD127loTreg细胞在外周血中约占CD4+T细胞的6.52％～6.97％,不同性别表达差异无显著性.结论 初步确定广州地区学龄前健康儿童CD4+CD25nt/hiCD127loTreg细胞在外周血中的正常范围,为临床研究儿童相关疾病提供参考依据.应用IL-7受体细胞膜表面标志物CD127联合检测外周血CD4+CD25nt/hiCD127loTreg细胞,能较好地反映完整的调节性Treg细胞.     

CD4+CD25+ regulatory T cells in health and disease

1. Over the past 5 years, tremendous progress has been made in understanding the suppressive mechanisms of T regulatory (Treg) cells. The Treg cells, a subpopulation of T cells, have been shown to play an important role in maintaining peripheral tolerance and the prevention of autoimmunity. 2. Various populations of Treg cells have been described, including thymically derived CD4(+)CD25(+) Treg cells. These naturally occurring Treg cells are present in the periphery and are capable of suppressing proliferation and effector T cell responses both in vitro and in vivo. 3. In addition, a second subset of Treg cells, type 1 T regulatoary (Tr1) and Th3 cells, exert their suppressive capacity via cytokines such as interleukin-10 and transforming growth factor-beta and are contact independent. 4. The present review summarizes the characteristics and molecular basis of CD4(+)CD25(+) Treg cells, as well as their therapeutic potential in modulating inflammatory diseases, such as inflammatory bowel disease and rheumatoid arthritis.     

Differential effects of single dose FTY720 on CD62L+ B-cells in stable renal allograft recipients

FTY720, a sphingosine-1-phosphate receptor agonist, is the archeotype of a new class of immune modulators, which redirects lymphocytes from the peripheral blood into secondary lymphatic tissue. Previously, it was shown that FTY720 differentially decreases peripheral T-cells, expressing specific chemokine and adhesion receptors. Here, we investigated the effect of single doses FTY720 on peripheral B-cells expressing CD62L, CD11a, CD49d and CXCR4 in stable human renal allograft recipients. Peripheral blood lymphocytes were isolated by Ficoll density centrifugation and stained with monoclonal antibodies against CD3 or CD19 and CD62L, CD11a, CD49d, CXCR4 to determine the percentage of these T- and B-cell subpopulations. Total lymphocyte counts were measured by routine laboratory diagnostics to calculate absolute lymphocyte subset counts. In FTY720 treated patients, total lymphocyte counts decreased by 31.8% (0.25-2 mg) and 60.4% (3.5 mg), and total T-cell counts by 38.8% (0.25-2 mg) and 70.9% (3.5 mg). In comparison, total B-cell counts decreased by 32.2% (0.25-2 mg) and 61.1% (3.5 mg). The reduction of CD62L+ B-cells was less pronounced as compared to CD62L+ T-cells (0.25-2 mg: 15.7% vs. 57.3%; 3.5 mg: 57.2% vs. 86.9%). CD11a+ B-cells decreased by 15.4% (0.25-2 mg) and 57.1% (3.5 mg), and CD49d+ B-cells by 15.0% (0.25-2 mg) and 56.7% (3.5 mg). CXCR4+ B-cells decreased by 19.9% (0.25-2 mg) and 57.2% (3.5 mg). In vitro experiments showed that FTY720 did not change the mean expression of CD62L, CD11a, CD49d and CXCR4 on CD19+ B-cells. In conclusion FTY720 treatment reduces B-cells expressing CD62L to a significant lesser degree than T-cells expressing CD62L.     

Comparison of azathioprine and mycophenolate mofetil for the prevention of acute rejection in recipients of pancreas transplantation

The study was performed to compare the efficacy and side effects of azathioprine (AZA) and mycophenolate mofetil (MMF) in conjunction with cyclosporine or tacrolimus and steroids for the prevention of acute pancreas rejection during the first 6 months of pancreas transplantation. In this case-controlled study, MMF is compared with historical controls of AZA in the prevention of acute pancreas rejection. The primary measures of treatment efficacy were patient and pancreas survival rate at 6 months after transplantation. Secondary efficacy measures were the occurrence of biopsy-proven pancreas rejections and the use of antilymphocyte preparations for rejection treatment. A total of 111 pancreas transplant patients (57 in the AZA group and 54 in the MMF group) were evaluated. The 6-month patient survival rate was 96% in the AZA group versus 97% in the MMF group (p = 0.57). The 6-month pancreas graft survival rate was 88% in the AZA group versus 91% in the MMF group (p = 0.29). However, biopsy-proven rejection episodes during the first 6 months of transplantation were significantly lower with MMF (46%) than with AZA (69%) (p = 0.01). In addition, patients in the AZA group received a greater number of full courses of antilymphocyte therapy as a rejection treatment (p = 0.004). Overall, the frequency of adverse events was similar, although the MMF group experienced higher incidences of gastrointestinal adverse events. In conclusion, compared with AZA, MMF significantly reduces the rate of biopsy-proven pancreas rejection during the first 6 months of transplantation and is well tolerated, except for gastrointestinal adverse events.