辅助性T淋巴细胞因子在大肠癌手术治疗前后的作用

目的：检测大肠癌患者手术前后外周血辅助性T淋巴细胞因子的变化,探讨辅助性T淋巴细胞因子1/辅助性T淋巴细胞因子2（Th1/Th2）比值异常的意义。方法空腹抽取45例大肠癌患者（试验组）手术前、后的外周血和20例健康志愿者（对照组）外周血,运用ELISA法和流式细胞技术检测白介素-2（IL-2）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和白介素-4（IL-4）、白介素-6（IL-6）、白介素-10（ IL-10）及Th1/Th2比值并进行比较。结果试验组及不同Ducks分期患者术前IL-2、IFN-γ、TNF-α外周血浓度均显著低于对照组（ P ＜0膊．05）,IL-4、IL-6、IL-10外周血浓度均显著高于对照组（ P ＜0．05）,Th1/Th2比值较对照组差异有统计学意义（ P ＜0．05）;试验组Ducks分期Ⅲ、Ⅳ期患者术前IFN-γ显著高于Ⅱ期患者（ P ＜0．05）,IL-4显著低于Ⅱ期患者（ P ＜0．05）,Th1/Th2比值较II期患者术前差异有统计学意义（ P ＜0．05）。试验组术后IL-2、TNF-α和IFN-γ的水平较术前显著升高（ P ＜0．05）, IL-4、IL-6和IL-10水平较术前显著降低（ P ＜0．05）, Th1/Th2比值较术前差异有统计学意义（ P ＜0．05）。试验组术后IL-2、TNF-α和IFN-γ显著低于对照组（ P ＜0．05）,试验组Ⅲ、Ⅳ期患者术后Th1/Th2比值较试验组Ⅱ期患者及对照组均差异有统计学意义（ P ＜0．05）。结论大肠癌患者手术前外周血中Th1类细胞因子IL-2、IFN-γ、TNF-α水平显著下降,Th2类细胞因子IL-4、IL-6、 IL-10表达显著升高, Th1/Th2比值下降,机体免疫调定点向免疫耐受方向漂移,使机体对体内癌细胞免疫识别机免疫清除能力下降;大肠癌手术后Th1类细胞因子外周血水平显著升高,Th2类细胞因子外周血水平明显降低,Th1/Th2比值趋向正常状态,机体的免疫识别及免疫清除能力增强,机体的抗肿瘤机能有所恢复;大肠癌晚期患者较正常对照组和Ⅱ期大肠癌患者的Th1细胞免疫功能受损更严重。     

海洛因依赖者血清中辅助性T细胞因子的表达水平及其临床意义

目的研究海洛因依赖者血清中辅助性T细胞1（Th1）／Th2类细胞因子的表达水平,进而对海洛因依赖者的免疫状况进行评价。方法选择2012年7月至2013年6月于温州市三蝉强制隔离戒毒所收容的50例海洛因依赖者作为海洛因依赖组,选择同期于我院行健康体检的50例正常人作为正常对照组。采取放射免疫法检测2组受试对象血清中白细胞介素2（IL-2）、γ干扰素（IFN-γ）、肿瘤坏死因子α（TNF-α）、TNF-β、IL-4、IL-6、IL-8、IL-10和IL-17的表达水平。结果海洛因依赖组血清中Thl细胞因子IL-2、IFN-γTNF—α和TNF-β水平均明显低于正常对照组[分别为（1184-38）ng／L比（249±76）ng/L、（2634±78）ng/L比（492±154）ng／L、（103±22）ng/L比（121±23）ng／L、（72±26）ng／L比（118±34）ng／L],差异均有统计学意义（t=3．154,t=4．518,t=2．459,t=3．089,均P〈0．05）;Th2细胞因子IL-4、IL-6、IL-8、IL-10和IL—17的表达水平均明显高于正常对照组[分别为（252±72）ng/L比（124±32）ng／L、（4．4±1．6）ng/L比（2．8士1．0）ng／L、（409±112）ng／L比（214±67）ng／L、（12．14±3．4）ng／L比（8．2±2．0）ng/L、（1644±50）ng／L比（954-28）ng／L],差异均有统计学意义（t=3．157,f=2．589,t=3．872,t=2．711,t=3．255,均P〈0．05）。结论海洛因依赖者血清中Th1／Th2类细胞因子水平较正常对照严重失衡,提示其免疫功能较差,易获得外界感染,需给予足够重视。     

三七总皂苷对调节性T细胞再分化为辅助性T细胞的影响

目的 考察三七总皂苷(PNS)调控调节性T细胞(Treg)再分化为辅助性T细胞17(Th17)的作用。方法 分离C57/BL6小鼠脾细胞,并磁珠分选出CD4⁺T细胞,进行体外培养,采用CCK-8法筛选PNS合适的给药浓度。建立Treg再分化为Th17的细胞模型,采用流式细胞术检测PNS对Treg再分化体系中Th17细胞分化比例的影响,酶联免疫吸附法检测体系上清中Th17特征性细胞因子白细胞介素(IL)-17A的水平,实时荧光定量聚合酶链式反应检测Th17特征性转录因子RORγt mRNA及炎症因子IL-17 mRNA的表达。结果 PNS可显著降低Treg再分化体系中CD4⁺IL-17⁺Th17细胞的比例和IL-17A的分泌水平,抑制ROR-γt mRNA和IL-17 mRNA的表达。结论 一定浓度的PNS可抑制Treg再分化为Th17,调控Treg/Th17平衡,进而防治类风湿关节炎等炎症免疫性疾病的发生和发展。     

匹多莫德口服液对小儿支原体肺炎外周血辅助性T细胞/CD4+CD25+Treg的影响北大核心CSCD

目的研究匹多莫德对小儿支原体肺炎Th17/CD4+CD25+Treg的影响。方法用随机数表将65例患儿分为试验组33例和对照组32例。2组均采用阿奇霉素进行序贯治疗,试验组额外给予匹多莫德口服液0.4 g·d^(-1),共治疗2周。对比2组患儿的临床疗效和药物不良反应(ADR)。抽取患者肘静脉血,用流式细胞法测定Th17/CD4+CD25+Treg,用酶联免疫吸附实验测定血清白细胞介素-17A(IL-17A)、转化生长因子β1(TGF-β_1)水平,用荧光定量PCR实验测定单个核细胞的维A酸相关孤独受体γt(RORγt)与叉头蛋白3(Foxp3)的mRNA表达。结果治疗后,试验组的有效率为90.9%(30例/33例),高于对照组的62.5%(20例/32例),差异有统计学意义(P<0.05)。治疗后,试验组Th17/CD4+CD25+Treg、IL-17A/TGF-β1及RORγt/Foxp3分别为0.97±0.18,1.25±0.21,1.49±0.21,对照组分别为1.25±0.20,1.69±0.26,1.68±0.18,试验组均低于对照组,差异均有统计学意义(P<0.01,P<0.05)。试验组与对照组ADR发生率分别为21.2%(7例/33例)和18.8%(6例/32例),2组差异无统计学意义(P>0.05)。结论匹多莫德能够调节支原体肺炎患儿Th17/CD4+CD25+Treg平衡,是其免疫学机制的重要组成部分。     

肺炎支原体感染对支气管哮喘病儿外周血1、9、17型辅助性T细胞及相关细胞因子水平的影响

目的 分析肺炎支原体(MP)感染对支气管哮喘病儿外周血辅助性T细胞1型(Th1)、辅助性T细胞9型(Th9)、辅助性T细胞17型(Th17)及相关细胞因子水平的影响。方法 选取2015年1月至2018年1月安阳市人民医院收治的164例支气管哮喘病儿,其中MP感染78例(MP阳性组),无MP感染86例(MP阴性组),另选取同期入院体检的健康儿童50例(对照组),比较三组病儿入院时外周血Th1、Th9、Th17及相关细胞因子[γ-干扰素(IFN-γ)、白介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)]水平,比较不同肺炎支原体抗体(MP-IgM)滴度、不同哮喘发作期病儿上述指标水平,分析MP-IgM滴度与各指标相关性。结果 MP阳性组外周血Th1[(0.59±0.07)%]低于MP阴性组、对照组,MP阳性组Th9[(1.93±0.20)%]、Th17[(2.94±0.26)%]、IFN-γ[(74.16±7.62)%]、IL-18[(220.16±23.46) ng/mL]、TNF-α[(0.58±0.06)ng/mL]水平高于MP阴性组、对照组,差异有统计学意义(P＜0.05);MP阳性病儿中,随MP-IgM滴度增加,Th1呈下降趋势,而Th9、Th17、IFN-γ、IL-18、TNF-α上升(P＜0.05);MP阳性病儿中,急性发作期Th1低于缓解期,急性发作期Th9、Th17、IFN-γ、IL-18、TNF-α高于缓解期(P＜0.05);支气管哮喘伴MP感染病儿MP-IgM滴度与外周血Th1呈负相关,与Th9、Th17、IFN-γ、IL-18、TNF-α呈正相关(P＜0.05)。结论 MP感染可影响支气管哮喘病儿外周血Th1、Th9、Th17及相关细胞因子水平,尤其在MP-IgM滴度高、急性发作期病儿中这种变化明显。     

初发过敏性紫癜和紫癜性肾炎患儿滤泡辅助性T细胞变化初探

目的:探讨滤泡辅助性T(Tfh)细胞在儿童初发过敏性紫癜(HSP)、紫癜性肾炎(HSPN)中的变化及其可能机制。方法:选择初发HSP患儿45例,采用流式细胞术检测外周血CD4+CXCR5+ICOS+ T细胞(Tfh细胞) 的比例,荧光实时定量聚合酶链反应(RT-PCR)检测转录因子Bcl-6、Blimp-1的mRNA表达,酶联免疫吸附试验(ELISA)法检测IL-21、IL-4血浆浓度。密切随访HSP患儿6个月。6个月时,根据是否有肾脏受累分为HSPN组19例和HSP组26例。另选取20例健康体检儿童为对照组。结果:(1)HSP组患儿Tfh细胞比例高于正常对照组(3.75%±1.32% vs 2.01%±0.72%,P<0.05);HSPN组患儿Tfh细胞比例高于HSP组(5.86%±1.94% vs 3.75%±1.32%,P<0.05);(2)Tfh细胞正性转录调节因子Bcl-6 mRNA表达HSPN组高于HSP组(P<0.05),均高于正常对照组(P<0.05);负性调节因子Blimp-1 mRNA表达HSPN组低于HSP组(P<0.05),均低于正常对照组(P<0.05);(3)Tfh细胞相关细胞因子IL-21血浆浓度HSPN组高于HS 组(P<0.05),均较正常对照组增高(P<0.05)。抑制Blimp-1表达的IL-4血浆浓度HSPN组和HSP组均高于正常对照组(P<0.05),但HSPN组和HSP组比较差异无统计学意义(P>0.05)。结论:Tfh细胞过度活化可能参与HSP免疫发病机制,Tfh细胞高表达可能是导致HSP患儿肾脏损害的原因之一。     

自身免疫性甲状腺炎小鼠发病中调节性T细胞、Th17细胞的变化

目的观察高碘诱发自身免疫性甲状腺炎(AIT)动物模型中CD4+CD25+调节性T细胞、Th17细胞的变化。方法选取NOD.H-2h4雌鼠饮0.005%碘化钠水,HE染色观察淋巴细胞浸润情况并进行甲状腺炎症程度评分;测定血清甲状腺球蛋白抗体(TgA b)水平;免疫荧光染色流式细胞仪分析CD4+CD25+Foxp3+调节性T细胞、Th17细胞比例的变化;实时定量RT-PCR检测Foxp3 mRNA、IL-17 mRNA、RORγt mRNA表达水平。结果 NOD.H-2h4小鼠高碘饮水后,甲状腺炎的发生率明显高于对照组,甲状腺组织有不同程度的淋巴细胞浸润,甲状腺相对重量及血清TgA b水平均较对照组小鼠明显升高(P<0.05)。脾细胞中CD4+CD25+Foxp3+调节性T细胞所占比例和Foxp3 mRNA表达量均较对照组明显降低(P<0.01);脾细胞中Th17细胞所占比例和IL-17 mRNA表达量、RORγt mRNA表达水平均较对照组明显升高(P<0.05)。结论 NOD.H-2h4小鼠在高碘诱导发生甲状腺炎时,脾脏CD4+CD25+调节性T细胞比例明显降低,Th17细胞比例明显升高。     

扩张型心肌病大鼠Th细胞活性及中药地肤子的干预作用

目的探讨扩张型心肌病(DCM)大鼠辅助性T(Th)细胞的活性变化以及地肤子对Th细胞的调节作用。方法 46只Wistar大鼠随机分为正常对照组(A组,10只)、DCM模型组(B组,12只)、地肤子5mg/g干预组(C组,12只)和地肤子20mg/g干预组(D组,12只)。8周后,超声检测各组大鼠心功能参数,HE、VG染色观察心肌组织病理学改变,ELISA法检测血浆和外周血单个核细胞(PBMC)培养上清液中白细胞介素4(IL-4)、γ干扰素(IFN-γ)水平。结果 D组大鼠心功能参数、心肌组织病理学变化较B组有明显改善。与A组相比,B、C、D组血浆和PBMC培养上清液中IFN-γ水平降低,而IL-4水平升高(P<0.05);D组上清液中IFN-γ和IL-4水平与B组比较差异有统计学意义(P<0.05)。结论大剂量地肤子干预可能会逆转DCM大鼠Th1/Th2细胞活性失衡,从而减轻免疫反应对心肌的损害。     

免疫 T细胞亚群水平及血清因子水平与再生障碍性贫血的相关性分析

目的：探讨免疫 T细胞亚群水平及血清白介素-2（ IL-2）、肿瘤坏死因子α（ TNF-α）、干扰素-γ（ IFN-γ）、可溶性凋亡相关因子（ sFas）与再生障碍性贫血（ AA）之间的相关性。方法选取该院100例AA患者作为观察组,另选取同期的100例健康者作为对照组。比较分析2组人群的免疫T细胞亚群水平及血清IL-2、TNF-α、IFN-γ、sFas的水平。结果观察组CD3＋、CD4＋、CD4＋/CD8＋及sFas 显著低于对照组（P＜0．05）,血清IL-2、TNF-α、IFN-γ及CD8＋明显高于对照组（ P＜0．05）;观察组中急性患者 CD3＋、CD4＋、CD4＋/CD8＋及 sFas 低于慢性患者（ P＜0．05）,血清IL-2、TNF-α、IFN-γ及CD8＋高于慢性患者（P＜0．05）。结论免疫T细胞亚群水平及血清IL-2、TNF-α、IFN-γ、sFas与AA之间存在一定的相关性,且能反映出一定的疾病严重程度。     

吉西他滨对宫颈癌患者辅助性T细胞17/CD4+CD25+调节性T细胞及肿瘤相关巨噬细胞的影响及意义

目的 分析吉西他滨对宫颈癌患者外周血辅助性T细胞17(Th17)/CD4+CD25+调节性T细胞(CD4+CD25+Treg)及肿瘤相关巨噬细胞的影响,为完善其药理机制提供数据支撑。方法 将陕西中医药大学第二附属医院2014年12月至2016年12月收治的59例拟行手术治疗的宫颈癌患者采用随机数字表法分为观察组30例和对照1组29例,两组均给予三维适形放疗和手术切除,观察组在此基础上给予吉西他滨新辅助化疗。另取11例同期入院体检的健康志愿者为对照2组,观察组和对照1组分别于治疗前后取患者空腹肘静脉血,对照2组于体检时取空腹肘静脉血,采用流式细胞法测定Th17与CD4+CD25+Treg的外周血细胞计数,采用酶联免疫吸附测定试剂盒测定白细胞介素-17A(IL-17A)、白细胞介素-17F(IL-17F)、白细胞介素-10(IL-10)及转化生长因子(TGF-β1)的血清水平。并于手术时留取病灶组织与癌旁健康组织,采用免疫组织化学实验测定肿瘤相关巨噬细胞表达水平。结果 (1)治疗前,观察组、对照1组和对照2组的Th17细胞计数分别为(4.75±0.63)%、(5.14±0.66)%和(12.02±1.85)%;CD4+CD25+Treg细胞计数分别为(13.41±1.52)%、(12.05±1.45)%和(7.52±0.88)%;治疗后,观察组、对照1组的Th17细胞计数分别为(16.52±3.02)%和(11.02±2.06)%,CD4+CD25+Treg细胞计数分别为(3.08±0.44)%和(6.11±0.74)%,与治疗前相比,差异有统计学意义(P<0.05)。(2)治疗后,观察组、对照1组血清IL-17A、IL-17F、IL-10及TGF-β1水平与治疗前相比,IL-17A与IL-17F水平有所升高,IL-10与TGF-β1水平有所下降,且观察组变化幅度高于对照1组,两组间差异有统计学意义(P<0.05)。 (3)观察组和对照1组病灶组织的肿瘤相关巨噬细胞表达量为(1.82±0.14)和(2.25±0.46),健康组织分别为(0.38±0.17)和(0.35±0.16),病灶组织高于健康组织,观察组高于对照1组,组间差异有统计学意义(P<0.05)。结论 吉西他滨能够抑制宫颈癌患者Th17/CD4+CD25+Treg漂移和肿瘤相关巨噬细胞活性,可能是其发挥抗癌作用的重要机制之一。     

特应性皮炎患者外周血辅助性T细胞22的表达及意义

[目的]检测特应性皮炎(AD)患者外周血辅助性T细胞22(Th22)的表达,探讨其在AD发病机制中的作用.[方法]以湿疹面积及严重度指数(EASI)评分评估患者病情,采用流式细胞术检测46例AD患者和28例健康对照者外周血Th22(IL-22)细胞,ELISA法检测血清中IL-22、IFN-γ、IL-4水平.[结果]AD患者外周血Th22细胞(2.35±0.64)％,明显高于对照组的(0.94±0.43)％(P＜ 0.01); Th22细胞与血清中IL-22呈正相关(r=0.48,P＜0.05),而与IFN-γ、IL-4无相关(r=- 0.105,P＞0.05;r=- 0.267,P＞0.05),Th22细胞与疾病的EASI评分呈正相关(r=0.53,P＜0.05).[结论]Th22细胞有可能作为监测AD严重程度或病情波动的指标.     

Reduced inflammatory responses of follicular helper T cell promote the development of regulatory B cells after Roux‐en‐Y gastric bypass

Bariatric surgery is currently the most effective strategy in treating severe obesity and its comorbidities, such as type 2 diabetes (T2D). However, the mechanism through which bariatric surgery mediates its benefits is not completely understood. Since obesity and T2D represent yet another inflammatory disease, and follicular helper T (Tfh) cells play important roles in inflammatory disorders, we investigated whether the Tfh activity was altered after Roux‐en‐Y gastric bypass (RYGB), one of the most common bariatric surgery procedures. We found that the Tfh cells after RYGB were not significantly changed in number, but presented altered cytokine secretion profile, including lower interferon (IFN)‐γ, interleukin (IL)‐2, IL‐4, and IL‐17 secretion. Tfh cells after RYGB also downregulated inducible co‐stimulator and programmed death‐1. Interestingly, after Tfh cell‐naive B cell coculture, Tfh cells after RYGB secreted more IL‐10 than autologous Tfh cells before RYGB. The frequencies of IL‐10‐expressing and transforming growth factor (TGF)‐β‐expressing regulatory B cells after Tfh cell‐naive B cell coculture were directly correlated with the frequency of IL‐10‐expressing Tfh cells. Depletion of IL‐10 in the coculture, however, resulted in fewer regulatory B cells. Finally, patients with greater increase in IL‐10‐expressing Tfh cells presented further reductions in body mass index, glycaemia, and body fat percentage. Together, these data demonstrated that the Tfh cells after RYGB presented lower inflammatory status and secreted higher IL‐10, through which these Tfh cells promoted the development of regulatory B cells. Higher IL‐10‐expressing Tfh cell level also predicted better patient response to RYGB.     

Th17／Treg 失衡在肝纤维化中的研究进展

肝纤维化是一种机体的慢性炎症反应,其特征是细胞外基质（ECM）合成与降解的失衡,从而造成肝内 ECM的病理性沉积,导致肝功能紊乱,最终发展为肝硬化,甚至是肝癌。肝纤维化的发病机理目前尚未清楚。随着免疫学的发展,T 细胞在肝纤维化的发病过程中的作用逐步得到认识,Th17细胞与 Treg 细胞这两种 T 细胞亚型在肝纤维化的发病过程中的作用已逐渐被认可。因此,该文就这两种细胞以及这两种细胞的相互作用在肝纤维化过程中的研究进展进行综述。     

Bcl-2 Knockdown Accelerates T Cell Receptor-Triggered Activation-Induced Cell Death in Jurkat T Cells

Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expression. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed Bcl-2 expression increased caspase-3 and diminished nuclear factor kappa B (NF-κB) translocation.     

Venom components of the scorpion Centruroides limpidus modulate cytokine expression by T helper lymphocytes: Identification of ion channel-related toxins by mass spectrometry

The study of the effector mechanisms of T helper cells has revealed different phenotypic characteristics that can be manipulated for designing new therapeutic schemes in different pathological scenarios. Ion channels are significant targets in T lymphocyte modulation since they are closely related to their effector activity. Remarkably, some toxins produced by scorpions specifically affect the function of these membrane proteins. For that reason, these toxins are important candidates in the search for new immunomodulators. Here, the effect of two venom fractions of the scorpion Centruroides limpidus was assessed on T lymphocyte proliferation and cytokine production. The venom fractions ClF8 and ClF9 were separated by reversed-phase high-performance liquid chromatography (RP-HPLC) and cultured at 25 and 35 µg/ml with murine T lymphocytes. The results indicate that the fraction ClF8 increased both production and secretion levels of IFN-γ, IL-4, IL-17A and IL-10 by CD4⁺ T cells at 24 h. In contrast, fraction ClF9 only promoted the secretion of IL-17A and IL-10 at its highest concentration (35 µg/ml). Both fractions did not show any effect on T cell proliferation. Subsequent analyses by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed seventeen toxins in the fraction ClF8 and five toxins in the fraction ClF9, most of them with voltage-gated sodium (NaScTx) and potassium (KScTx) channels as molecular targets. These toxins might probably interact with ion channels involved in T lymphocyte activity. Our findings suggest that the difference in composition between the two fractions could be related to the observed effects, and the components identified could be isolated to search for possible immunomodulatory molecules.     

Modulating the function of T cell immunoglobulin mucin cell surface proteins for therapeutic immunoregulation

Brigham & Womens Hospital, Beth Israel Hospital: WO2005033144 and WO2005090573

T cell immunoglobulin-mucin (TIM) molecules are transmembrane cell surface glycoproteins possessing an immunoglobulin domain and a mucin-like domain in their extracellular region. Recently, several of these molecules have been shown to be differentially expressed by the T helper (T_H)-1 and T_H2 lymphocyte subsets, which are known to differ in their cytokine production and effector functions and to play crucial roles in coordinating immune responses and controlling or promoting the development of autoimmune and allergic diseases. Such TIM proteins, including TIM-1, -2, -3 and -4 in mice, have therefore been regarded as potential regulators of T_H1 and T_H2 activities and immune responses. The two patent applications reviewed show that TIM-1 and TIM-2 are both associated with T_H2 cells, whereas TIM-3 is associated with T_H1 cells, and that TIM-4 and galectin-9 are ligands for TIM-1 and TIM-3, respectively. Furthermore, various reagents targeting these TIM proteins are demonstrated to affect immune functions in experimental murine models. Thus, TIM-1 or -2 modulation selectively altered T_H2-mediated responses, whereas TIM-3 modulation influenced T_H1-mediated responses. Hence, it is claimed that the manipulation of TIM protein functions may provide novel methods for therapeutic immunoregulation in the treatment of immune-based diseases. However, further studies are needed to examine the validity of this claim in human disease situations.     

Pharmacoimmunodynamics of methylprednisolone: Trafficking of helper T lymphocytes

A two-compartment dosed model was used to characterize the cell trafficking behavior of helper T cells in response to various single doses of methylprednisolone. Steroids are assumed to inhibit the circadian-determined cell return from extravascular sites to blood in a classic inhibitory pattern reflected by an IC₅₀.The rate of cell efflux from tissues is modeled with a cosine function having a period of 24 hr and a maximum at about 1 am. Nonlinear leastsquares regression employing differential equations was used to analyze helper T-cell data from three human studies from our laboratory. The IC₅₀ value of methylprednisolone of 12–19 ng/ml approximates receptor K_D values. Simulations were performed to demonstrate the log-linear role of steroid dose or AUCon the integral of effect of helper T cells over a wide range of methylprednisolone doses. This pharmacodynamic model allows flexibility for characterizing any type of steroid dosing regimen and is relevent in describing complex response data for corticosteroid immunosuppressive effects in man.Supported in part by grant GM 24211 from the National Institutes of General Medical Sciences, National Institutes of Health.     

T细胞受体信号转导通路的动力学分析

目的:建立T细胞受体信号转导途径的动力学模型,通过模型仿真揭示T细胞受体信号途径各分子间的动态调控过程,简要分析模型的动力学特性。方法:根据数据库KEGG及相关中英文文献,提取T细胞受体信号转导各条通路相关分子作用的方式及数量关系,利用Matlab7.0的Simulink工具箱构建信号途径的动力学模型并仿真。结果:模型仿真结果与文献符合得较好,能够从数量上反映T细胞受体信号转导途径中各分子间复杂的调控关系,并能通过模型仿真发现和验证该信号途径中的关键节点分子。结论:模型基本反映了T细胞受体信号转导途径的动力学特征,可以作为后续的精确定量关系研究的基础。     

免疫相关性全血细胞减少症患者骨髓Th细胞比例及功能变化

目的探讨免疫相关性全血细胞减少症（IRP）患者骨髓中辅助性T淋巴细胞（Th）亚群数量、功能改变及在发病中的作用。方法用流式细胞术同期对照研究16例正常对照组、15例初诊IRP组、24例再生障碍性贫血（AA）组、14例骨髓增生异常综合征（MDS）组骨髓Th细胞改变情况;RT-PCR方法检测10例正常人、25例初诊IRP患者、9例AA患者、9例MDS患者未经体外刺激的骨髓单个核细胞（BMMNC）中Th1细胞的代表因子IFN-γ、IL-2和Th2细胞的代表因子IL-4、IL-10的基因表达。结果（1）骨髓中Th1细胞、Th2细胞及Th1／Th2比值正常对照组为0．42％、0．24％和1．57;初诊IRP组为0．58％、1．95％和0．31;AA组为4．42％、0．41％和21．22;MDS组为0．44％、0．84％和0．96。IRP组Th1细胞与正常对照组及MDS组无显著差异（P〉0．05）,显著低于AA组（P〈0．01）;但IRP组Th2细胞显著高于正常对照组、AA组（P〈0．01）,与MDS组差异未达统计学意义（P=0．054）。IRP组骨髓中Th2细胞占优势,Th1／Th2比值显著低于正常对照组、MDS组及AA组（P〈0．01）。（2）与正常对照组比较,初诊IRP组Th2型细胞因子IL-4、IL-10 mRNA表达明显增高（P〈0．01）,而Th1型细胞因子IFN-γ、IL-2mRNA表达无显著增高（P〉0．05）;AA组Th1型细胞因子显著增高（P〈0．01）,而Th2型无区别;MDS组未见细胞因子表达增高。结论IRP患者骨髓Th2细胞亚群增多,Th细胞平衡向Th2偏移,且Th2型细胞因子表达增高,细胞功能亢进,可能是IRP免疫发病环节之一,也表明IRP是一种不同于AA和MDS的全血细胞减少症。     

Th 细胞亚群在肺纤维化小鼠中的动态表达

目的：研究辅助性T细胞亚群（Th17、Th1和Th2）在肺纤维化模型小鼠的动态表达。方法40只雄性C57／BL6小鼠随机均分为两组,分别经气管一次性注入生理盐水（A组）或博来霉素溶液0.04ml（5mg／kg,B组）,于第3、7、14和28天处死。采用HE和Masson染色评价小鼠肺组织病理形态变化;检测肺组织中羟脯氨酸（HYP）含量;应用流式细胞术分析脾脏中Th1、Th2和Th17细胞的动态变化。结果A组小鼠肺泡形态正常,肺组织HYP含量无明显变化。B组小鼠第7天时即有部分肺泡结构破坏,肺组织可见大量炎性细胞及红细胞浸润,伴细束状胶原纤维增生;第7、14、28天肺组织HYP含量高于A组（P＜0．05）;与A组比较,B组4个时间点的Th17和Th2细胞数增加,Th1细胞数减少（P＜0．05）。结论Th17、Th2和Th1细胞与特发性肺纤维化密切相关,可能参与其发病机制。