腹腔镜子宫肌瘤剔除术对Th1/Th2细胞平衡的影响

目的:为了探讨腹腔镜子宫肌瘤剔除术对Th1/Th2细胞平衡的影响。方法:择期子宫肌瘤患者4 0例,分别采用腹腔镜手术和常规开腹手术,测定术前、术后2、2 4、4 8小时Th1、Th2细胞数量及血清IL 18、IL 10水平。结果:两组术后2小时均出现Th1/Th2细胞平衡向Th2反应转换,Th1细胞、Th1/Th2比值、IL 18下降(腹腔镜组:P <0 0 5 ,P <0 0 1,P <0 0 5 ;开腹组:P <0 0 1,P <0 0 1,P <0 0 1) ,而Th2细胞、抗炎因子IL 10上升(腹腔镜组:P <0 0 1,P <0 0 1;开腹组:P <0 0 1,P <0 0 1)。但腹腔镜组术后2 4小时各项指标即恢复,而开腹组各项指标的变化与术后2小时类似,并持续至术后4 8小时。结论:腹腔镜子宫肌瘤剔除术对Th1/Th2细胞平衡影响小,恢复快,优于开腹手术。     

安脑片对aGVHD小鼠Th1/Th2细胞的调节作用

目的:观察中药安脑片对aGVHD小鼠的Th1/Th2细胞的调节作用。方法:清洁级BALB/c雄性小鼠作为供鼠,以清洁级C57BL/6雌性小鼠为受鼠,建立aGVHD模型;C57BL/6小鼠在移植前进行60Co全身照射,剂量为9.0 Gy,照射后4小时内尾静脉输注BALB/c雄性小鼠的骨髓细胞8×107个/只+脾细胞8×107个/只。造模成功后,随机分为安脑片组和空白组。移植后第30天杀鼠取材,取眶静脉血并制备肝脏标本,ELISA法检测小鼠血清IFN-γ及IL-10水平,免疫组化法检测肝脏组织IFN-γ及IL-10的阳性表达。结果:安脑片组小鼠血清IFN-γ的表达治疗前为(9.67±0.88)pg/ml,治疗后降至(4.81±0.87)pg/ml,IL-10的表达在治疗前为(3.81±0.55)pg/ml,治疗后升至(8.16±0.92)pg/ml。免疫组化的结果也显示小鼠肝脏组织IFN-γ及IL-10的表达改善明显,治疗后小鼠IFN-γ的表达评分降为1.27±0.46,IL-10的表达评分升至3.73±0.46,与治疗前相比差异显著(P=0.000)。结论:安脑片可有效改善小鼠aGVHD效应并调节Th1/Th2细胞因子的平衡。     

CpG ODN对rHBsAg免疫小鼠Th1/Th2型免疫应答的影响

目的：初步探讨CpC寡脱氧核苷酸(CpG ODN)与重组乙型肝炎表面抗原(rHBsAg)联合免疫小鼠的Th1／Th2型免疫应答效应。方法：BALB／c小鼠经后腿胫骨前肌免疫2次，ELISA法检测血清乙型肝炎表面抗体(抗-HBs)IgG亚类IgG2a/IgG1的比值；生物活性法检测脾细胞诱生上清中的IFN-γ和IL-2含量；ABC-ELISA法检测小鼠血清中IL-4、IL-10及IL-12含量。结果：加CpG ODN组与单独注射rHBsAg组相比：抗-HBs IgG亚类IgG2a／IgG1比值明显高；Th1型细胞因子IFN-γ和IL-2的表达增强，抑制Th2型细胞因子IL-4和IL-10的产生。结论：CpCODN能够明显增强rHBsAg免疫小鼠Th1型抗体亚类IgG2a的产生，并且诱导Th1型细胞因子的表达，抑制Th2型细胞因子的表达。     

Graves’病患者Th1/Th2免疫应答及性激素对Th1/Th2的影响（文献综述）

Graves’病（GD）是最常见的自身免疫性甲状腺疾病（AITD），其发病机理以体液免疫异常为大家所熟知，但细胞因子在GD中的发病作用越来越受到国内外学者的重视，研究的焦点主要侧重于Th1／Th2细胞平衡紊乱。GD及其他自身免疫性疾病女性显著高发，提示性激素是影响机体免疫功能的重要因素。本文就近年来国内外对GD患者Th1／Th2免疫应答的研究及性激素对Thl／Th2平衡的影响作一综述。     

HBcAg/HBeAg对慢性乙型肝炎患者PBMC中Th1/Th2类细胞应答的影响

目的 探讨ＨＢｃＡｇ／ＨＢｅＡｇ对慢性乙型肝炎患者ＰＢＭＣ中Ｔｈ１／Ｔｈ２类细胞应答的影响。方法 用套式ＰＣＲ法检测６４便慢性ＨＢＶ感染者ＰＢＭＣ中ＨＶＢ ＤＮＡ;分别用ＰＨＡ、ＨＢｃＡｇ和ＨＢｅＡｇ体外培养;ＥＬＩＳＡ法检测ＰＢＭＣ产生Ｔｈ１类细胞因子（ＩＬ－２、ＩＦＮ－γ）和Ｔｈ２类细胞因子（ＩＬ－４、ＩＬ－１０）的含量。结果 表明ＨＢＶ ＤＮＡ阳性组和阴性组相比,无论是在ＰＨＡ还是在ＨＢｃＡ     

急性MCMV感染对小鼠脾Th1/Th2/Th17细胞亚群分化的影响

目的:在整体水平观察小鼠巨细胞病毒(MCMV)感染对小鼠脾Th1/Th2/Th17细胞亚群分化及其主要的效应性细胞因子(IFN-γ、IL-4、IL-17A)表达的影响.方法:建立MCMV感染模型,8只BALB/c小鼠分别于接种MCMV Smith株后3天和14天各处死4只;另设8只接种唾液腺匀浆的模拟感染小鼠作为对照.用空斑形成试验测定肝、脾和唾液腺组织病毒滴度;流式细胞术检测脾T淋巴细胞中Th1(CD4+ IFN-γ+)、Th2(CD4+ IL-4+)、Th17(CD4+IL-17A+)细胞比例,双抗体夹心ELISA法检测脾细胞培养上清中病毒特异性IFN-γ、IL-4、IL-17A水平.结果:MCMV感染早期肝、脾和唾液腺组织中病毒呈低水平复制,而感染后14天仅在唾液腺组织呈高水平复制;Th1细胞比例及病毒特异性IFN-γ主要在MCMV感染早期呈显著升高(P ＜0.01);Th2细胞及IL-4均无明显表达及改变;Th17细胞及病毒特异性IL-17A则主要在感染后14天升高(P＜0.05).结论:MCMV感染早期,机体通过上调Th1细胞分化比例及IFN-γ的表达发挥抗病毒效应,而MCMV诱导Th17细胞分化及IL-17A的高表达可能是MCMV感染致宿主特异性细胞免疫功能失调并逃避机体特异性细胞免疫攻击的原因之一.     

Th1和Th2细胞在体内的分化

近年来，人们对Th1/Th2细胞在体内的分化及其调控等方面有了许多新的认识。本文就Th1/Th2细胞在体人的分化来源、基因转录和信号调节、影响因素、表面标志及应用方面作一综述，这对进一步探讨免疫系统及其功能具有重要意义。     

TLSFJM对Th1/Th2样细胞亚群比率的影响

目的 :探讨TLSFJM 对同种异体抗原活化的Th1/Th2样细胞亚群变化的影响。方法 :在混合淋巴细胞反应 (MLR)体系中加入TLSFJM 或IL 4 ,用细胞内免疫荧光染色结合流式细胞术分析TLSFJM 对Th1/Th2样细胞亚群比率的影响。结果 :在TLSFJM实验组中 ,活化淋巴母细胞分化为IFN γ 细胞的比率略有降低 (49.8%→ 4 3.1% ) ,IL 4 、IL 6 细胞的比率有明显降低 ,IL 4 细胞的比率由 75 .4 %降至 4 3.7% ,IL 6 细胞的比率由6 7.8%降至 5 2 .6 %。在未活化小淋巴细胞中 ,也观察到同样的趋势。结论 :TLSFJM 对Th1、Th2样细胞亚群都有抑制 ,但似乎主要作用于Th2样细胞亚群 ,从而使其在Th1/Th2样细胞的比例降低     

Th1／Th2与慢性乙型肝炎

慢性乙型肝炎发病机制复杂，与机体的免疫状态密切相关，CD4^ Th细胞是机体的重要调节细胞，根据其产生细胞因子的不同分为Th1和Th2亚型，分别参与调节细胞免疫和体液免疫，Th1和Th2可相互调节，影响免疫应答的格局，Th1／Th2在多种感染性疾病中发挥重要作用，慢性乙肝患者存在Th1／Th2失衡，本文就Th1／Th2与慢性乙肝的关系研究进展进行简述。     

Th1／Th2细胞在炎症浸润中的不同表现

Th细胞向外周组织的浸润是局部炎症部位极化免疫的首要条件。Th细胞向外浸润过程中表达了不同的受体以适应不同的需要，Th1细胞优先表达P－和E－选择素配体、CHCR3、CCR5、粘合素α6β1等分子；Th2细胞则优先表达CCR3、CCR4、CCR8等分子，导致它们在炎症浸润过程中具有不同的外渗潜力，产生不同的局部炎症反应，而且它们之间也可通过负性调节来互相抑制对方。     

Murine lupus in MRL/lpr mice lacking CD4 or CD8 T cells

MRL/lpr mice develop a systemic autoimmune disease similar to systemic lupus erythematosus in humans. The mice show progressive lymphadenopathy due to the accumulation of an unusual population of CD4^?8^?(DN) B220⁺ αβ⁺ T cells. We bred MRL/lpr mice with mice lacking CD4⁺ or CD8⁺ T cells by gene targeting via homologous recombination in embryonal stem cells to determine the roles of these cells in the autoimmune disease. No difference in survival or autoantibody levels was noted between CD8-/- lpr and littermate controls. Interestingly, these CD8-/- lpr mice have a reduced level of B220⁺ DN T cells despite the fact that the degree of lymphadenopathy was unaltered. CD4-/- lpr mice had a diminished autoimmune disease with a reduction in autoantibody production and skin vasculitits, and increased survival compared to littermate controls. However, CD4-/- lpr mice had an enhanced splenomegaly that developed massively by 16–20 weeks of age (5 to 8 greater than lpr control mice) due to the accumulation of DN B220⁺ T cells. In addition, there were no differences in peripheral lymph node enlargement, although the proportion of DN B220⁺ T cells was about twofold higher in the CD4-/- lpr mice. These cells were phenotypically identical to the DN population in control lpr mice, indicating that the accumulating DN T cells can be dissociated from the autoimmune disease in these mice. Collectively, our results reveal that the autoimmune disease is dependent on CD4⁺, but not CD8⁺ T cells, and that many of the B220⁺ DN T cells traverse a CD8 developmental pathway.     

TNF-like weak inducer of apoptosis promotes blood brain barrier disruption and increases neuronal cell death in MRL/lpr mice

Neuropsychiatric disease is one of the most common manifestations of human systemic lupus erythematosus, but the mechanisms remain poorly understood. In human brain microvascular endothelial cells in vitro, TNF-like weak inducer of apoptosis (TWEAK) decreases tight junction ZO-1 expression and increases the permeability of monolayer cell cultures. Furthermore, knockout (KO) of the TWEAK receptor, Fn14, in the MRL/lpr lupus mouse strain markedly attenuates neuropsychiatric disease, as demonstrated by significant reductions in depressive-like behavior and improved cognitive function. The purpose of the present study was to determine the mechanisms by which TWEAK signaling is instrumental in the pathogenesis of neuropsychiatric lupus (NPSLE). Evaluating brain sections of MRL/lpr Fn14WT and Fn14KO mice, we found that Fn14KO mice displayed significantly decreased cellular infiltrates in the choroid plexus. To evaluate the integrity of the blood brain barrier (BBB) in MRL/lpr mice, Western blot for fibronectin, qPCR for iNOS, and immunohistochemical staining for VCAM-1/ICAM-1 were performed. We found preserved BBB permeability in MRL/lpr Fn14KO mice, attributable to reduced brain expression of VCAM-1/ICAM-1 and iNOS. Additionally, administration of Fc-TWEAK intravenously directly increased the leakage of a tracer (dextran-FITC) into brain tissue. Furthermore, MRL/lpr Fn14KO mice displayed reduced antibody (IgG) and complement (C3, C6, and C4a) deposition in the brain. Finally, we found that MRL/lpr Fn14KO mice manifested reduced neuron degeneration and hippocampal gliosis. Our studies indicate that TWEAK/Fn14 interactions play an important role in the pathogenesis of NPSLE by increasing the accumulation of inflammatory cells in the choroid plexus, disrupting BBB integrity, and increasing neuronal damage, suggesting a novel target for therapy in this disease.     

雌二醇对系统性红斑狼疮小鼠模型肾组织芳香酶表达的影响

目的：研究雌二醇对系统性红斑狼疮（ Systemic lupus erythematosus, SLE）小鼠模型肾组织芳香酶表达的影响。方法：BALB／c小鼠卵巢切除后采用ConA活化的同系脾细胞诱导SLE，同时给予不同剂量苯甲酸雌二醇，并设立对照组。于4、6、8和10周用ELISA法检测外周血和肾组织雌二醇（Estradiol，E2）水平，RT-PCR检测肾组织芳香酶mRNA的表达。结果：SLE模型小鼠外周血和肾组织E2水平随着外源性给予苯甲酸雌二醇剂量的加大而升高，与未进行SLE模型诱导的小鼠相比较，SLE模型鼠外周血和肾组织E2水平升高（P〈0．05）；正常BALB／c小鼠肾组织芳香酶mRNA低表达；随着SLE炎症的诱导及E2水平的升高，肾组织芳香酶mRNA的表达增加。结论：E2通过促进SLE小鼠模型肾组织芳香酶mRNA的表达影响SLE发生发展。     

Selective silencing of DNA-specific B lymphocytes delays lupus activity in MRL/lpr mice

The pathological DNA-specific B lymphocytes in lupus are logical targets for a selected therapeutic intervention. We have hypothesized that it should be possible to suppress selectively the activity of these B cells in lupus mice by administering to them an artificial molecule that cross-links their surface immunoglobulins with the inhibitory FcgammaIIb surface receptors. A hybrid molecule was constructed by coupling the DNA-mimicking DWEYSVWLSN peptide to a monoclonal anti-mouse FcgammaRIIb antibody. This chimeric antibody was added to cultured spleen cells from sick MRL/lpr mice, immunized with diphtheria toxoid, resulting in reduction of the numbers of anti-DNA but not of anti-diphtheria IgG antibody-producing cells. Intravenous infusions with the DNA-peptide antibody chimera to 7-wk-old animals prevented the appearance of IgG anti-DNA antibodies and of albuminuria in the next 2 months. The administration of the DNA-peptide chimeric antibody to 18 wk-old mice with full-blown disease resulted in the maintenance of a flat level of IgG anti-DNA antibodies and in delay of the aggravation of the lupus glomerulonephritis. The use of chimeric antibodies targeting inhibitory B lymphocyte receptors represents a novel approach for the selective suppression of autoreactive disease-associated B cells in autoimmune diseases.     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

系统性红斑狼疮患者个性的艾森克量表评定

本文采用 EPQ 对45名 SLE 患者和45名正常对照者进行1∶1配比病例对照研究,结果表明,内倾个性的人发生 SLE 的机遇高于无内倾个性的人3.16倍;具有不稳定型个性的人发生 SLE 的机遇高于稳定个性的人3.40倍。     

系统性红斑狼疮病人血T,B淋巴细胞Bcl—2的表达

目的：探讨Ｂｃｌ－２在系统性红斑狼疮（ＳＬＥ）发病机制中作用。方法：采用流式细胞仪双标记法检测３１例ＳＬＥ病人外周血Ｔ、Ｂ细胞Ｂｃｌ－２蛋白表达。结果：发现活动期ＳＬＥ病人活动期ＳＬＤ病人ＣＤ３＾＋、ＣＤ４＾＋和ＣＤ８＾＋Ｔ细胞Ｂｃｌ－２蛋白表达明显高于非活动期ＳＬＥ病人、其他疾病组和正常对照组。ＣＤ１９＾＋Ｂ细胞Ｂｃｌ－２蛋白表达在各组之间并无统计学差异。ＣＤ３＾＋Ｔ细胞Ｂｃｌ－２蛋白表达的平均     

Th1, Th2, and Th17 cytokines in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the breakdown of immune tolerance leading to excessive inflammation and tissue damage. Imbalance in the levels of cytokines represents one of the multifactorial causes of SLE pathogenesis and it contributes to disease severity. Deregulated levels of T helper type 1 (Th1), type 2 (Th2), and type 17 (Th17) cytokines have been associated with autoimmune inflammation. Growing evidence has shown deregulated levels of Th1, Th2, and Th17 cytokines in SLE patients compared to healthy controls associated with disease activity and severity. In this review, we describe and discuss the levels of Th1, Th2, and Th17 cytokines in SLE patients, and clinical trials involving Th1, Th2, and Th17 cytokines in SLE patients. In particular, with the exception of IL-2, IL-4, and TGF-β1, the levels of Th1, Th2, and Th17 cytokines are increased in SLE patients associated with disease severity. Current phase II or III studies involve therapeutic antibodies targeting IFN-α and type I IFN receptor, while low-dose IL-2 therapy is assessed in phase II clinical trials.