Changes of Regulatory T Cells in Graves' Disease

The immune mechanism of Graves' diseases (GD) and the roles of regulator T cells were investigated. In 32 patients with GD (GD group) and 20 healthy volunteers (control group), flow cy-tometry was used to detect the proportion of CD4 CD25 cells, MACS to isolate CD4 CD25 cells, RT-PCR to assay the expression of FOXP3, and ELISA to test the level of IL-10, respectively. It was found that there was no significant change in the proportion of CD4 CD25 T cells between GD group and control group (P>0.05), while secretion of IL-10 and expression of FOXP3 in GD group were lower than control group (P<0.01 and P<0.05, respectively). In conclusion, though the proportion of regulatory T cells of peripheral blood lymphocytes in the patients with GD, the functions of them were significantly weakened, which might be a pathogenic factor in GD.     

Involvement of CD4^＋CD25^＋ regulatory T cells in the pathogenesis of polycythaemia vera

Background Regulatory T cells （mreg） have been shown to play an important role in the regulation of hematopoietic activity. However, there is no information about the effect of Treg cells in the pathogenesis of polycythaemia vera （PV）. Methods In this study, we investigated the percentage and function of Treg cells in the peripheral blood of 21 PV patients and 25 healthy donors, mreg cells were identified and characterized as CD4^＋CD25^＋FOXP3^＋ by flow cytometry. The suppressive activity of CD4^＋CD25^＋ Treg cells was assessed by the proliferation and cytokine secretion of the co-cultured CD4^＋CD25^- fractions. Results The results showed that the percentage of Treg cells in the peripheral blood of PV patients significantly increased compared to healthy controls （（10.93±4.02）% vs （5.86±1.99）%, P 〈0.05）. Moreover, the mRNA and protein expression of FOXP3 was higher in CD4^＋CD25^＋ Treg cells. Coordinately, when co-cultured with the activated CD4^＋CD25^- cells, the CD4^＋CD25^＋ Treg cells showed enhanced suppressive function in PV. Yet, the underlying mechanism for the increased frequency and function of CD4^＋CD25^＋ Treg cells is still to be clarified. Conclusion Treg cells expansion might account for the abnormal T cell immunity in PV patients and thus contribute to the pathogenesis of PV.     

Role of interleukin-10 and transforming growth factor beta 1 in otitis media with effusion

Background Otitis media with effusion （OME） is a disease with complicated pathogeneses which are not clearly known Increasing interest has been focused on immunological cells, cytokines and their roles in chronic inflammatory states. This study was designed to disclose the existence and roles of interleukin-10 （IL-10） and transforming growth factor beta1 （TGF-β1） in the cause of OME in adults, and to investigate the probable role of Foxp3^＋CD4^＋CD25^＋ T cells in OME. Methods The concentrations of IL-10 and TGF-β1 in the middle ear effusions （MEEs） and plasmas of 36 adults （45 ears） with OME were measured by means of enzyme linked immunosorbent assay （ELISA）. As contrast, the concentrations of IL-10 and TGF-131 in the plasma of 30 normal volunteers were measured using the same method. Furthermore, the proportion of Foxp3^＋CD4^＋CD25^＋ T cells in CD4^＋ T cells of blood was tested by flow cytometry. Results （1） The concentrations of IL-10 in all MEEs and plasmas of the chronic OME patients were higher than those in patients with acute OME （both P 〈0.05）, so was TGF-131 （both P 〈0.01）. The concentration of IL-10 in MEEs was significantly higher than that in plasmas, not only in acute OME （P〈0.01）, but also in chronic OME （P〈0.01）. In chronic OME, the concentration of TGF-β1 in MEEs had no statistical difference with those in plasmas of the same patients. However, the concentration of TGF-β1 in plasmas of patients with chronic OME was significantly higher than that in plasmas of normal volunteers （P 〈0.01）. （2） The concentrations of IL-10 and TGF-β1 in MEEs of the patients who had been treated more than once were higher than those MEEs of the patients who were treated for the first time, respectively （P〈0.05, P〈0.01）. The level of TGF-β1 in plasmas of the patients who had been treated more than once was higher than in those of the patients who were treated firstly （P 〈0.05）, while the level of IL-10 in plasmas had no difference. The concentration of IL-10 in mucoid MEEs was higher than those in serous ones （P〈0.05）, while TGF-β1 had no statistical difference between mucoid and serous MEEs （P〉0.05）. The concentration of IL-10 in MEEs had a strong correlation with the duration of the illness （r=0.547, P〈0.01）. The same correlation was also found between the concentration of TGF-β1 in MEEs and the times patients being treated （r=0.579, P 〈0.01）. （3） The proportion of Foxp3^＋CD4^＋CD25^＋T/CD4^＋ T cells in the blood of chronic OME was not only significantly higher than that in the acute OME （P〈0.01）, but also higher than that in normal volunteers （P 〈0.01）. In chronic OME, there was a correlation between the proportion of Foxp3^＋CD4^＋CD25^＋ T/CD4^＋ T cells in the blood and the concentration of IL-10 in the plasmas （r=0.602, P 〈0.05）. Conclusions IL-10 and TGF-β1, as two important immunoregulatory mediators, participate in middle ear inflammatory response, especially in chronic course of OME in adults. Foxp3^＋CD4^＋CD25^＋ T cells may play some immunoregulatory roles in the course of this disease.     

Changes of CD4＋ CD25＋ Regulatory T Cells in Peripheral Blood in Patients with Hepatocellular Carcinoma Before and after TACE

This study investigated the changes of CD4＋ CD25＋ regulatory T cells （Tregs） in periph-eral blood of patients with hepatocellular carcinoma before and after transcatheter arterial chemoem-bolization （TACE）. The proportion of CD4＋ CD25＋ Tregs among CD4＋ T lymphocytes in peripheral blood of 33 patients with hepatocellular carcinoma was determined by flow cytometry before, 1 week and 1 month after TACE. And 25 healthy volunteers served as control. One month after TACE, the patients were divided into two groups： 22 in group A, who were in stable condition or getting better; and 10 in group B, who were deteriorating. One patient died and was excluded. The results showed that the percentage of CD4＋CD25＋ Tregs among CD4＋ T lymphocytes did not significantly change in the 33 patients 1 week after TACE as compared with that before TACE, however, the difference was significant （P〈0.01） between the patients with hepatocellular carcinoma and the healthy subjects. The percentage of CD4＋ CD25＋ Tregs among CD4＋ T lymphocytes in group A 1 month after TACE was decreased significantly in comparison with that before and 1 week after TACE （P〈0.01）, whereas, that in group B was increased significantly 1 month after TACE （P〈0.01）. It was concluded that patients with hepatocellular carcinoma had a higher proportion of CD4＋CD25＋ Tregs in peripheral blood. TACE did not significantly affect the level of CD4＋ CD25＋ Tregs within short time （such as 1 week）. The proportion of CD4＋CD25＋ Tregs in peripheral blood 1 month after TACE was related to the prognosis of hepatocellular carcinoma.     

Correlation between elevated FOXP3 expression and increased lymph node metastasis of gastric cancer

Background FOXP3 was thought to express in the T-cell lineage exclusively until recently when FOXP3 was shown to be expressed by cancer cells. It was indicated that FOXP3 may play a wider role in biology by endowing tumor cells with immune suppressive activity. However, researches between FOXP3 and lymph node metastasis of gastric cancer were relatively infrequent, so the present work was aimed to investigate the relationship between FOXP3 expression and lymph node metastasis in human gastric cancer.Methods A total of 122 gastric cancer patients were enrolled in this study, and gastric tumor specimens and lymph nodes were acquired. Thirty patients who had chronic superficial gastritis diagnosed by gastroscopy contemporaneously in the Peking University People＇s Hospital were chosen randomly as the control group. Immunohistochemistry was performed to evaluate FOXP3 expression. A survival analysis on the 122 patients was then performed. Then, NCI-N87cell lines were used to confirm FOXP3 expression in gastric carcinoma cells. Finally, evaluation of FOXP3 expression in gastric tumor and peritumor tissues in 12 patients were conducted using immunohistochemistry and Western blotting. A X2 test or Fisher＇s exact test （bilateral） was conducted to compare the percentage of positive percentage staining between groups. Kaplan-Meier analysis was performed for survival analysis.Results FOXP3 was expressed by gastric cancer cells and peritumor epithelial cells. FOXP3 expression was increased in primary tumors （58.2%） than that in control group （26.7%）. In the lymph-node metastasis group, the incidence of lymph node metastasis which was less than 60% had a significant upregulation of FOXP3 in primary tumors and lymph nodes.However, the frequency of FOXP3 expression had no relationship with survival.Conclusion FOXP3 probably has a relationship with lymph node metastasis of gastric cancer.     

Study on clinical effect and mechanism of Jianpi Qingre Huayu Recipe (健脾清热化瘀方) in treating patients with gastric ulcer

Objective： To study the effects of Jianpi Qingre Huayu Recipe （健脾清热化瘀方, JQH） in curing gastric ulcer and to preliminarily probe into its pathogenic mechanism, Methods： Fifty patients with gastric ulcer of Pi （脾）-insufficiency and stasis-heat syndrome type were assigned to the treated group （30 patients） and the control group （20 patients）. They were treated respectively with JQH and Ranitidine. At the same time, another group consisting of 20 healthy persons was set up for normal control. The clinical effect on gastroscopic figure and traditional Chinese medicine （TCM） syndrome were observed. Changes of T-cell subsets and interleukin-8 （IL-8） in serum as well as IL-8 in mucosa around the gastric ulcer were determined before and after treatment by flow cytometry and ELISA. Results： Comparison of the total effective rate on gastroscopic figure in the treated group and the control group （86.7% vs 80.0%） showed insignificant difference, but the cure rate and markedly effective rate in the former （50.0% and 20.0%） was higher than that in the latter （40.0% and 15.0%） respectively. Comparison of the total effective rate on TCM syndrome in the treated group and in the control group （96.7% vs 70.0%） showed insignificant difference, but the cure rate and markedly effective rate in the former （63.3% and 23.3%） was higher than that in the latter （50.0% and 20.0%） respectively. Serum levels of CD3^＋, CD4^＋, CD8^＋ got restored to normal range in the treated group after treatment but it was not so in the control group. IL-8 level in gastric mucosa was improved in both groups but the improvement in the treated group was better. Cenclusien： JQH could effectively treat gastric ulcer and partly reduce its recurrence through improving patients＇ immune function.     

Influence of Danshen Injection on airway inflammation and CD4^＋CD25^＋ regulatory T cells of asthmatic rats

Objective： To investigate the influence of Danshen Injection on airway inflammation and CD4^＋CD25^＋ regulatory T cells（CD4^＋CD25^＋ Tr） of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods： 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids （BALF） were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain （HE）. Flow cytometry was used to detect the CD4^＋CD25^＋ Tr ratio in peripheral blood mononuclear cells （PBMCs）. Results： Total cell, the percentage of lymphocytes, neutrophils and eosinophils （Eos） in BALF of Danshen Injection-treated group were lower than that in asthma group （P〈0.05, P〈0.01）. Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4^＋CD25^＋ Tr of asthma group was lower than that of control and Danshen Injection treated group （P〈0.05）. Conclusion： Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4^＋CD25^＋ Tr.     

Assessment of the number and function of macrophages in the placenta of gestational diabetes mellitus patients

In order to assess the number and function of macrophages in the placenta of pregnancy complicated with gestational diabetes mellitus （GDM） as well as those of normal pregnancies, placenta samples were collected from 15 GDM patients （GDM group） and 10 normal pregnant women （control group）. The expression levels of macrophage markers （CD68/CD14） and inflammatory cytokines （IL-6/TNF-α） in placenta were detected using immunohistochemistry and PCR. The results showed that the number of CD68＋ or CD14＋ cells in the GMD group was remarkably higher than that in the control group （P〈0.05）, indicating that the number of macrophages in the GDM group was significantly greater than that in the control group. The mRNA expression levels of CD68＋, IL-6 and TNF-α were higher in the GMD group than in the control group. In conclusion, more macrophages accumulate in placenta of pregnancy complicated with GDM, and the expression levels of pro-inflammation factors are also in- creased in GDM pregnancies, suggesting that macrophages and inflammatory mediators （IL-6 and TNF-α） mav olav an imoortant role in GDM.     

前列腺素E2对CD4+CD25+调节性T细胞免疫功能影响的实验研究

目的 探讨前列腺素E2对CD4+CD25+调节性T细胞免疫功能的影响。 方法 分离正常BALB/c小鼠脾脏CD4+CD25+ Treg,利用固相包被抗CD3和加入可溶性CD28辅助活化,予以PGE2刺激。根据刺激剂量不同,分成对照组、A (7 μmol/L)、B (14 μmol/L)、C (28 μmol/L)组,观察PGE2对Treg的增殖、IL-10、IL-2分泌和Foxp3表达的影响。 结果 PGE2刺激12 h,3组细胞较对照组增殖反应差异均无统计学意义(P＞0.05);B、C组IL-2表达显著降低(P＜0.05),而Foxp3表达明显升高(P＜0.05);C组IL-10分泌升高(P＜0.05);刺激24 h,B、C组细胞增殖反应较对照组显著增强(P＜0.05);A、B、C组IL-2分泌均下降(P＜0.05),而Foxp3表达均升高(P＜0.05);C组IL-10分泌升高(P＜0.05);刺激72 h,3组增殖反应、IL-10以及Foxp3表达均显著升高(P＜0.05),而IL-2分泌下降(P＜0.05)。 结论 PGE2能直接增强CD4+CD25+ Treg的免疫抑制功能,从而可能进一步对效应T细胞免疫功能产生影响。      

双歧三联活菌胶囊治疗溃疡性结肠炎的疗效及其对CD4+CD25+调节性T细胞和IL-10的影响

目的 探讨双歧三联活菌胶囊辅助治疗溃疡性结肠炎(UC)的临床疗效及其对CD4+CD25+调节性T细胞和IL-10的影响.方法 选取溃疡性结肠炎患者87例,采用随机数表法分为观察组45例和对照组42例.对照组给予抗生素及5-氨基水杨酸制剂奥沙拉嗪钠胶囊进行常规对症治疗,观察组在常规对症治疗基础上加用双歧三联活菌胶囊治疗.比较两组患者治疗前后的结肠炎症评分、CD4+CD25+调节性T细胞和IL-10变化及临床疗效.结果 治疗后观察组的总有效率为86.67%,明显高于对照组的69.05%,差异有统计学意义(P<0.05);治疗前两组结肠症状评分比较差异无统计学意义(P>0.05),治疗后观察组结肠症状评分明显低于对照组,差异有显著统计学意义(P<0.01);治疗前两组CD4+CD25+调节T细胞占CD4+T细胞比例及IL-10水平值比较差异均无统计学意义(P>0.05),治疗后观察组CD4+CD25+调节T细胞占CD4+T细胞比例及IL-10水平均明显高于对照组,差异均有显著统计学意义(P<0.01).结论 歧乳杆菌三联活菌胶囊辅助治疗UC患者疗效确切,且CD4+CD25+调节性T细胞比例及IL-10水平均有明显升高,在改善患者肠道内微生物平衡中具有显著作用,值得推广应用.     

系统性红斑狼疮患者外周血CD4+ CD39+ T细胞中FOXP3蛋白的表达及糖皮质激素对其影响

目的 研究系统性红斑狼疮(SLE)患者外周血CD4+ CD39+ T细胞中FOXP3蛋白的表达情况,以及糖皮质激素治疗的影响.方法 采用流式细胞术检测47例SLE患者(其中29例为初发未经治疗的活动期SLE)和22名正常人外周血CD4+ CD25+ CD39+ T细胞、CD4+CD25+ FOXP3+ T细胞及CD4+ CD39+ FOXP3+ T细胞百分率以及FOXP3蛋白的表达,分析3组细胞之间的相关性及糖皮质激素治疗的影响.结果 SLE活动组、缓解组、正常对照组外周血CD4+ CD25+ CD39+ T细胞百分率分别为(1.3±0.5)%、(1.9±0.8)%、(2.3±1.0)%,该群细胞在SLE活动组中的表达水平低于缓解组和正常对照组(均P<0.05),而在后2组之间差异无统计学意义(P>0.05);SLE活动组中CD4+ CD25+、CD4+ CD25high及CD4+ CD39+ T细胞表达的FOXP3蛋白百分率分别为(45±12)%、(65±14)%、(70±14)%,FOXP3蛋白在CD4+ CD39+ T细胞和CD4+ CD25highT细胞中的表达水平明显高于在CD4+CD25+T细胞中的表达水平(P<0.01),而在CD4+ CD39+T细胞与CD4+CD25highT细胞中的表达水平差异均无统计学意义(均P>0.05).结论 CD39可能是调节性T细胞较好的表面标记,CD39+ Treg细胞表达异常可能参与SLE的发病机制.     

CD4~+CD25~+FOXP3~+Treg细胞在高危多发性骨髓瘤治疗中预测复发及治疗意义

目的 探讨CD4+CD25+FOXP3+调节性T淋巴细胞(Treg)在高危多发性骨髓瘤治疗中预测复发及治疗意义。方法 选择2018年3月至2019年3月我院收治的126例高危多发性骨髓瘤患者为病例组,同期在我院体检健康者100例为对照组,比较病例组和对照组不同化疗疗效、不同复发情况患者外周血CD4+CD25+FOXP3+Treg细胞比例,用Spearman相关性分析CD4+CD25+FOXP3+Treg细胞比例与患者复发的相关性,用受试者工作特征曲线(ROC)分析CD4+CD25+FOXP3+Treg细胞比例预测患者复发的价值,并进行CD4+CD25+FOXP3+Treg细胞比例不同患者随访期间无进展生存的Kaplan-Meier分析。结果 病例组CD4+CD25+FOXP3+Treg细胞比例远高于对照组(P0.001);化疗无效患者CD4+CD25+FOXP3+Treg细胞比例远高于化疗有效患者(P0.001);复发患者CD4+CD25+FOXP3+Treg细胞比例远高于未复发患者(P0.001);CD4+CD25+FOXP3+Treg细胞比例与患者复发呈正相关(P0.05);CD4+CD25+FOXP3+Treg细胞比例预测患者复发的AUC(95%CI:0.759～0.856)为0.809,敏感性为62.80%,特异性为95.80%,准确性为89.30%,截断值为3.66%。CD4+CD25+FOXP3+Treg细胞比例3.66%组随访期间无进展生存率显著低于CD4+CD25+FOXP3+Treg细胞比例3.66%组(P0.05)。结论 CD4+CD25+FOXP3+Treg细胞比例在高危多发性骨髓瘤患者外周血中呈上升状态,其水平检测对于化疗后复发有一定预测价值,有助于临床预测化疗效果、监测早期复发及预后判断。     

糖皮质激素在实验性变态反应性脑脊髓炎中对调节性T细胞的作用

目的:研究糖皮质激素在实验性变态反应性脑脊髓炎(EAE)治疗中对调节性T细胞的调变作用. 方法:采用从新鲜牛脊髓中提取的髓鞘碱性蛋白(MBP)免疫诱导Balb/c小鼠成功诱发EAE后,分组注射糖皮质激素或者安慰剂,在采用指标评估基础上,分别采用流式细胞术和ELISA方法检测CD4 CD25 调节性T细胞特异性FOXP3和血中IL-10的表达水平. 结果:与对照组相比,糖皮质激素注射组小鼠发病程度轻,调节性T细胞特异性FOXP3和血中IL-10的表达水平均有明显差异. 结论:糖皮质激素可能通过增加调节性T细胞的数量及活性,减轻EAE的症状,为临床治疗多发性硬化(MS)提供理论基础.     

腺病毒介导的"睡美人"转座子与IL-10共表达对NOD小鼠Th17/Treg细胞平衡的影响

目的：观察腺病毒介导的"睡美人"（SB）转座子与白细胞介素10（IL-10）共表达对非肥胖糖尿病（NOD）小鼠脾细胞中Th17/Treg细胞平衡的影响,阐明IL-10对NOD小鼠的可能治疗机制。方法：提取C57BL6小鼠的脾细胞并培养,将脾细胞分为对照组、空载体组和治疗组。对照组脾细胞不做任何处理,空载体组将不含IL-10基因而有转座子序列的腺病毒载体和不含转座酶的腺病毒载体共同感染小鼠脾细胞,治疗组将含有IL-10基因和转座子序列的腺病毒载体以及含有转座酶的腺病毒载体共同感染小鼠脾细胞。感染48 h后RT-PCR法检测各组小鼠脾细胞中IL-10 mRNA表达水平。感染48 h后将上述3组处理的脾细胞分别种植到对照组、空载体组和治疗组NOD小鼠右后腿的腘窝皮下,每组6只小鼠,每周注射1次,共6次。注射结束后4周处死小鼠,ELISA法检测各组NOD小鼠血清中IL-10表达水平;流式细胞术检测各组NOD小鼠脾细胞中CD4+IL-10+、CD4+IFN-γ+、Th17和Treg细胞的比例。结果：与对照组和空载体组比较,治疗组C57BL6小鼠脾细胞中IL-10 mRNA表达水平明显升高（F=72.71,P<0.05）,NOD小鼠血清中IL-10表达水平明显升高（F=8.89,P<0.05）,NOD小鼠脾细胞中CD4+IL-10+细胞和Treg细胞比例明显升高（F=72.09,P<0.05;F=12.98,P<0.05）;但治疗组小鼠脾细胞中Th17细胞比例明显下降（F=6.39,P<0.05）;NOD小鼠脾细胞中CD4+IFN-γ+细胞比例在对照组、空载体组和治疗组之间比较差异无统计学意义（F=2.72,P>0.05）。结论：腺病毒介导的SB转座子与IL-10共表达后可以升高NOD小鼠血清中IL-10表达水平;同时可明显升高NOD小鼠脾细胞中CD4+IL-10+细胞比例,降低Th17细胞比例,升高Treg细胞比例,调控Th1/Th2和Th17/Treg的平衡,对NOD小鼠起到治疗作用。     

Treg细胞在骨髓增生异常综合征中的变化及其意义

目的 研究CD4+Treg细胞在骨髓增生异常综合征(MDS)中的变化及其意义.并探讨CD4+Treg细胞在MDS低危组和MDS高危组中的变化和内在联系.方法 流式细胞仪检测MDS低危组(21例)、MDS高危组(15例)及正常对照组(22例)CD4+CD25+T细胞和CD4+FOXP3+T细胞分别占CD4+T细胞的比例,采用直接免疫荧光法标记T细胞特征抗原.结论 CD4+FOXP3+T细胞占CD4+T细胞的比例在各组中比较:MDS低危组与高危组均明显高于正常对照组,MDS高危组高于低危组,差异有统计学意义,CD4+CD25+T细胞占CD4+T的比例在各组中无明显差异.结论CD4+Treg细胞在MDS组较正常对照组明显升高,并且随着疾病的进展CD4+Treg细胞逐渐升高.     

DNAM-1通过IL-2/STAT-5通路调节Ⅰ型调节性T细胞的增殖和功能

目的 探讨DNAM-1对Ⅰ型调节性T细胞（Tr1细胞）活化、增殖和功能的影响及相关分子机制。方法 利用anti-CD3/CD28激活小鼠T细胞,采用流式细胞术分别检测静息和激活状态下CD4+ T细胞和Tr1细胞DNAM-1分子表达变化;分离DNAM-1基因敲除小鼠（KO小鼠）脾脏初始CD4+ T细胞并体外诱导Tr1细胞,流式细胞术检测CD25和CD69活化分子表达水平,CFSE标记后检测增殖能力,IL-2刺激前后检测KO小鼠 Tr1细胞分泌IL-10和转录激活蛋白（p-STAT5）水平变化。结果 流式细胞术结果显示：与静息状态下相比较,激活状态的CD4+ T细胞和Tr1细胞表达DNAM-1分子均增高（P<0.05）;敲除DNAM-1不影响小鼠脾脏Tr1细胞的数量和比例,但KO小鼠Tr1细胞表达细胞激活分子CD25和CD69均降低,差异有统计学意义（P<0.05）;与WT小鼠比较,KO小鼠诱导型Tr1细胞体外增殖能力降低（P<0.05）;与WT组Tr1细胞比较,KO小鼠Tr1细胞分泌抑制性细胞因子IL-10水平降低（P<0.05）,给予IL-2刺激后仍无法逆转,表达Il-10 mRNA和Gzmb mRNA水平降低（P<0.05）;给予不同剂量IL-2刺激Tr1细胞后,KO小鼠Tr1细胞表达p-STAT5水平相比较WT组均降低（P<0.05）。结论 DNAM-1参与Tr1细胞的活化和增殖,并通过IL-2/STAT5信号通路影响Tr1细胞抑制功能。     

成人隐匿性自身免疫糖尿病CD4+调节性T细胞研究

目的 观察成人隐匿性自身免疫糖尿病(LADA)患者CD4+CD25+T细胞和CD4+ T细胞的FOXP3 mRNA表达,探讨其免疫学的发病机制.方法 LADA患者67例,2型糖尿病30例,正常对照30例,通过流式细胞术检测CD3+、CD4+、CD8+、CD4+ CD25+ T细胞阳性细胞百分率.采用磁珠分离CD4+T细胞,用实时-PCR方法,半定量检测CD4+T细胞的FOXP3 mRNA表达水平.结果 LADA患者比正常对照组,CD4+CD25+T细胞升高(4.1±1.9 vs 2.8±1.5,P＜0.01),CD4+CD25+T细胞占CD4+T细胞的比例升高(11.9±5.0 vs 8.2±3.7,P＜0.01).LADA患者CD4+T细胞FOXP3 mRNA的表达水平明显降低(0.52-fold,P＜0.01,n=10).结论 LADA患者存在调节性T细胞抑制功能缺陷.