老年肺癌患者IL-6、sIL-2R和T细胞亚群检测的临床意义

目的　探讨老年肺癌患者外周血 IL - 6、s IL- 2 R和 T细胞亚群活性的变化。方法　对老年肺癌患者化疗前、后及老年健康对照组应用流式细胞分析法测定 T细胞亚群 ,双抗体夹心法 (EL ISA)测定 IL - 6及 s IL- 2 R水平。结果　肺癌组 s IL - 2 R、IL- 6及 CD8高于对照组 (P<0 .0 5) ,而CD3 及 CD4水平低于对照组 ,化疗后 s IL - 2 R、IL- 6及 CD8水平明显下降 ,但仍高于对照组 ,CD3 及 CD4水平略升高 ,仍低于对照组。结论　 IL - 6、s IL-2 R及 T细胞亚群联合测定可以反映肺癌病人机体免疫功能状态 ,可作为判断疾病的预后和免疫调节治疗的客观指标。     

白塞病患者血清T淋巴细胞亚群和细胞因子变化初探

目的 探讨白塞病(BD)患者外周血T淋巴细胞亚群和细胞因子的变化。方法 用流式细胞仪和放射免疫法分别检测BD在患者血清T淋巴细胞亚群(CD3、CD4、CD8、CD16^ /CD56^ 、CD19)和细胞因子[白细胞介素(IL)-1β、IL-2、sIL-2R、IL-6、IL-8、肿瘤坏死因子(TNF)-α]的水平。结果 BD组CD8细胞显著高于对照组，CD4、CD4/CD8比值及自然杀伤细胞(NK)(CD16^ /CD56^ )细胞显著低于对照组，而CD3和CD19细胞两组间差异无显著性；BD组血清sIL-2R和IL-8水平显著高于对照组，而IL-1、IL-2、IL-6及TNF-α两组间差异无显著陛。结论 BD患者存在细胞免疫紊乱，血清sIL-2R和IL-8升高可能是疾病活动指标之一。     

毛细支气管炎患儿外周血T细胞亚群、IL-2及IL-6的检测及意义

目的探讨毛细支气管炎患儿外周血T细胞亚群、IL-2及IL-6的变化及意义。方法选择73例急性期呼吸道合胞病毒（RSV）毛细支气管炎患儿（毛细支气管炎组）和40例健康体检儿童（健康对照组）,采用免疫荧光法检测两组外周血T细胞亚群,ELISA法测定血清IL-2和IL-6。结果与健康对照组相比,毛细支气管炎组CD4＋水平和CD4＋/CD8＋比值增高,血清IL-2水平和IL-2/IL-6比值降低,IL-6水平增高。结论婴幼儿RSV毛细支气管炎与哮喘时T细胞亚群和Th1/Th2功能失调的表现类似。     

慢性丙型肝炎病毒感染状态与机体免疫功能关系的探讨

目的：探讨慢性丙型肝炎病毒感染患者HCVRNA增殖状态与T细胞亚群功能及血浆中IL-2和sIL-2R活性的关系。方法：以间接免疫荧光法，ELISA法和RT-PCR分别检测75名慢性HCV感染患者外周血T细胞亚群，IL-2及sIL-2R的水平和HCVRNA。结果：慢性HCV感染患者周围血CD3 ，CD4 淋巴细胞亚群，CD4 ／CD8 比值及IL-2水平均显著低于正常对照组(P<0.01)而sIL-2R明显升高(P<0.01)；血清HCVRNA阳性患者T细胞亚群，CD4 ／CD8 比值及IL-2水平显著低于HCVRNA阴性患者(P<0.01)。结论：慢性HCV感染患者的机体免疫功能紊乱，细胞免疫功能低下，HCVRNA阳性患者较阴性患者更甚，提示细胞免疫功能受抑可能是HCV持续增殖的原因。     

不同证型原发性肝癌T细胞亚群活性、肿瘤标志物水平关系的研究

近年来发现原发性肝癌(HCC)患者外周血T细胞亚群活性及血清肿瘤标志物水平均有明显异常.本文从中医角度,对不同证型(气虚血瘀证和气滞血瘀证)HCC患者外周血T细胞亚群CD3+、CD4+、CD8+活性及CD4+/CD8+比值和血清肿瘤标志物水平进行对比研究,以寻找HCC气血辨证规律.     

慢性肾炎患者外周血共刺激分子CD28和CD137水平变化研究

目的　研究慢性肾炎患者外周血共刺激分子CD2 8和CD1 37的表达特点及其在慢性肾炎免疫病理机制中的作用。方法　采用免疫荧光标记和流式细胞仪分析 ,对 5 2例慢性肾炎患者外周血共刺激分子CD2 8、CD1 37和T淋巴细胞亚群的表达进行检测。结果　慢性肾炎患者T细胞亚群明显失衡 ,表现为CD4减少 ,CD8增加 ,CD4 CD8比值显著降低。共刺激分子CD2 8表达显著低于正常对照组 (P <0 0 1) ,且CD+4 CD+2 8T细胞和CD+8CD+2 8T细胞均显著减少 (P <0 0 1)。共刺激分子CD1 37表达显著高于正常对照组 (P <0 0 1)。结论　慢性肾炎患者外周血T细胞亚群失衡和T细胞活化所必需的共刺激分子CD2 8、CD1 37异常表达 ,可能在慢性肾炎发生和病变进展中起着重要作用     

血液透析对尿毒症患者外周血T细胞亚群的影响

目的　探讨终末期尿毒症患者外周血T细胞亚群功能以及血液透析对其的影响。方法　应用流式细胞仪法检测 30例透析及未透析患者外周血T细胞表面的CD3、及其亚群CD4及CD8抗原表达。结果　尿毒症未透析组 (NHD组 )的外周血T细胞的CD3、CD4和CD8表达及CD4+ /CD8+ 比值均显著低于正常对照组 (P<0 0 5 ) ;透析组 (HD组 )与NHD组相比 ,其CD3、CD4和CD8值及CD4+ /CD8+ 比值均显著上升 (P <0 0 5 ) ,其中CD8值接近于正常对照组。结论　尿毒症患者的T细胞免疫功能明显失衡 ,血液透析疗法能够部分改善患者的T细胞亚群免疫功能。     

阿米巴肝脓肿患者红细胞免疫功能和血清中细胞因子水平的临床观察

目的 :观察阿米巴肝脓肿患者红细胞免疫功能和血清中细胞因子水平的变化。方法 :采用红细胞 C3b受体花环 ( RBC- C3b RR)及免疫复合物花环 ( RBC- ICR) ,分别计算其花环率 ,测定红细胞免疫功能 ;用双抗体夹心 EL ISA法测定可溶性白细胞介素 2受体 ( IL - 2 R)、肿瘤坏死因子( TNFα)、白细胞介素 6( IL- 6)及白细胞介素 8( IL- 8) ;用流式细胞仪测定外周血 CD4及 CD8细胞水平。结果 :4 0例患者血清 IL - 2 R( 672 .4 8± 2 91.52 U/ml)、TNFα( 0 .874± 0 .4 52 ng/ml)、IL - 6( 0 .198± 0 .0 2 1ng/ml)及 IL- 8( 0 .648± 0 .0 75ng/ml)均显著地高于健康人 ;RBC- C3b RR显著地低于健康人 ,并与 IL- 2 R呈负相关 ;部分患者外周血 T细胞亚群 ,显示 CD4细胞减少 ,CD8细胞增高 ,CD4 /CD8比值明显低于健康人。结论 :阿米巴肝脓肿患者红细胞和 T细胞的免疫功能均处于明显抑制状态。     

T淋巴细胞亚群及炎性细胞因子与慢性浅表性胃炎和十二指肠球部溃疡的关系

目的:检测慢性浅表性胃炎和十二指肠球部溃疡患者外周血T淋巴细胞亚群水平的变化及炎性细胞因子白细胞介素-6(IL-6)和白细胞介索-8(IL-8)的血清含量,分析其与幽门螺杆菌(Hp)的关系,探讨可能的发病机制.方法:收集91例经内镜检查证实慢性浅表性胃炎和十二指肠球部溃疡患者的血清标本,用流式细胞仪测T淋巴细胞亚群值,用酶联免疫吸附法(ELISA)检测IL-6和IL-8含量,并分析其与Hp的关系.结果:慢性浅表性胃炎和十二指肠球部溃疡患者外周血CD8及CD4/CD8与正常对照组比较差异有显著性(P＜0.01).血清IL-6含量与正常对照组比较差异有显著性(P＜0.01).血清IL-8含量与正常对照组比较差异有显著性(P＜0.01).Hp阳性者IL-6含量低于Hp阴性者(P＜0.01).Hp阳性者IL-8含量高于Hp阴性者.结论:慢性浅表性胃炎和十二指肠球部溃疡患者CD8细胞数较正常人显著升高,CD4/CD8比值较正常人显著降低.血清IL-6、IL-8含量明显增高.Hp阳性者IL-8含量增高而IL-6含量下降.     

CD4~+T细胞亚群Th1/Th2和Th17/Treg在卵巢癌中的分布及意义

目的探讨卵巢癌患者外周血中CD4~+T细胞亚群Th1/Th2和Th17/Treg及相关细胞因子的分泌及其意义。方法30例卵巢癌患者为研究组,20例健康体检者为对照组,采用流式细胞术、酶联免疫吸附法(ELISA)、RT-PCR检测两组外周血中Th1/Th2和Th17/Treg CD4~+T细胞亚群相关细胞因子、转录因子表达情况并对比。结果与对照组比较,研究组外周血中Th1细胞亚群降低,其分泌的相关细胞因子γ-干扰素(IFN-γ)、白细胞介素(IL)-2及T盒子21转录因子(T-bet)表达均显著降低(P0. 05);Th2,Th17,Treg细胞亚群比例均升高,其各自分泌的相关细胞因子IL-4、IL-5、IL-13,IL-17α、IL-17f、IL-21、IL-22,IL-10、IL-35、转化生长因子(TGF)-β及转录因子GATA3,维甲酸孤儿核受体家族(ROR)γt,叉头样转录因子(FOXP) 3表达均显著提高(均P0. 05)。结论卵巢癌患者外周血中Th1细胞亚群受到了抑制,Th2、Th17、Treg细胞亚群都得到促进,提示这些CD4~+T细胞亚群可以作为判断卵巢癌疾病进展的重要指标。     

Interleukin 7 stimulates tumour necrosis factor alpha and Th1 cytokine production in joints of patients with rheumatoid arthritis

BACKGROUND: A large number of activated T cells are found in the joints of patients with rheumatoid arthritis (RA). Interleukin 7 (IL7), a T cell growth factor and a regulator of Th1 and Th2 cytokine production, is produced by synoviocytes from patients with RA. OBJECTIVE: To investigate the effect on proinflammatory cytokine production of synovial fluid mononuclear cells (SFMC) and the mechanism by which IL7 influences CD4+ T cell activity in patients with RA. METHODS: In a cross sectional group of patients with RA, IL7 levels were compared with those of healthy controls and related to disease activity. The effect of IL7 on cytokine production was tested by RA SFMC and on SF CD4+ T cells in the presence of mononuclear cells (MC). Production of tumour necrosis factor alpha (TNF alpha), IL1 beta, interferon gamma (IFN gamma), and IL4 was measured by enzyme linked immunosorbent assay (ELISA) and by single cell FACS analysis. Expression of the IL7 receptor alpha chain on CD4+ T cells (essential for IL7 signalling) was assessed. Direct effects of IL7 on isolated synovial fluid (SF) CD4+ T cells were studied by cytokine analysis. By neutralisation of IL12 in MC cultures, indirect effects of IL7 on T cells through accessory cells were studied. RESULTS: IL7 serum levels were higher in patients with RA than in healthy controls and correlated positively with C reactive protein levels. IL7 stimulated TNFalpha production by SFMC and very potently stimulated IFN gamma and TNF alpha production by SF CD4+ T cells. These effects were probably mediated through the IL7 receptor alpha chain, which was abundantly expressed on SF CD4+ T cells. Besides the direct stimulation of T cell cytokine production by IL7, its action was partly dependent on IL12, indicating that IL7 also stimulates accessory cell function, leading to T cell activation. CONCLUSION: IL7 stimulates proinflammatory cytokine production of intra-articular CD4+ T cells and accessory cells from patients with RA. The correlation with measures of disease activity indicates that IL7 might substantially contribute to the perpetuation of Th1 and TNF alpha mediated proinflammatory responses in patients with RA.     

白介素-1 7在溃疡性结肠炎表达的研究

目的研究白介素-17(IL-17)在溃疡性结肠炎(UC)的表达和分泌及与疾病活动性的关系.方法用ELISA法测定UC患者及正常对照者血清或细胞培养液中,IL-17、IL-6和IL-8的浓度,逆转录聚合酶链反应(RT-PCT)测定IL-17mRNA的表达.结果32例UC患者外周血中IL-17,IL-6和IL-8的浓度与40例正常对照者比较,差异无显著性(P＞0.05),但外周血CD+4T细胞在PMA和抗CD3的刺激下,表达IL17mRNA及分泌IL-17的水平均明显高于对照组[(23.6±5.7)pg/ml和(13.1±3.2)pg/ml,P＜0.01].UC患者病变部位的黏膜固有层CD+4T细胞(LP-CD+4T)与非受累部位的LP-CD+4T细胞比较,它们表达大量的IL-17mRNA并自发分泌大量的IL-17蛋白,且IL-17浓度与该部位的单个核细胞(LPMC)分泌的IL-6,以及患者外周血中的C-反应蛋白,血沉均呈显著正相关.在刺激剂的作用下,病变部位的LP-CD+4T细胞IL-17的分泌进一步增加,且明显高于非受累部位LP-CD+4T细胞的分泌水平.另外,UC病变部位LPMC分泌的IL-6和IL-8的水平均明显高于非受累部位的LPMC,但在培养液中加入抗IL-17单克隆抗体后,LPMC细胞IL-6和IL-8的分泌均明显被抑制.结论UC患者病变部位的LP-CD+4T细胞表达和分泌IL-17明显增加,并与疾病的活动性呈正相关.抗IL-17抗体可明显抑制LMPC产生炎性细胞因子.IL-6和IL-8.结果说明,IL-17在UC肠道的炎症病理中起重要作用;阻断IL-17的分泌可能是治疗UC的一种有效手段.     

Treg/Th17平衡与血吸虫感染免疫

血吸虫感染可诱导调节性T细胞（Treg）和Th17型免疫反应。研究表明,Treg和Th17细胞及其平衡在血吸虫感染中具有非常重要的作用。Treg细胞抑制宿主体内过度病理反应,并有助于血吸虫逃避宿主的免疫攻击;而Th17细胞促进血吸虫感染过程中的免疫病理发展。本文就Treg/Th17平衡与血吸虫感染免疫关系的研究进展作一综述。     

Acute choriocapillaris occlusion in pregnancy and puerperium. Toxemias, thrombotic microangiopathies

Six cases of gravidic toxemia (4) and thrombotic thrombocytopenic purpura (Moschowitz's disease) in puerperium with choriocapillaris occlusion, were examined. At the acute stage, the vision is improved, ophthalmoscopy of the fundus revealed cystlike bullous exudative subretinal with retinal detachment, yellowish spots (of retinal pigment epithelium) and often minimal localized arteriolar narrowing. The evolution included retina application pigmentary disturbances and Elschnig's spots. Fluorescein angiography showed delayed filling of the capillaris and dye leakage in the subretinal space (first hypofluorescence and late hyperfluorescence). There are various stages of ischaemic involvement but in all cases visual symptoms may be due to central obstructive choroidopathy with delayed filling and occlusion. The retinal detachment in toxemia or Moschowitz disease in pregnancy in secondary to microcirculatory choroidal damage (short ciliary vessels essentially) with rupture of blood retinal barrier. Other constatations are made in disseminated intravascular coagulation, periarteritis nodosa, accelerated nephrosclerosis, hemolytic uremic syndrome in puerperium, and these suggested possible relationship between the various conditions.     

Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL-22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status

BACKGROUND: We analyzed the influence of Crohn's disease (CD)-associated IL23R gene variants on IL-22 that is expressed in IL-23R+ Th17 cells. METHODS: IL-22 serum levels were measured in 242 CD patients and in 31 healthy controls. Subanalyses included serum levels of IL-6, TNF-alpha, IL-17A, IL-17F, C-reactive protein (CRP), and leukocyte count. In all patients, genotyping for 10 CD-associated IL23R single nucleotide polymorphisms (SNPs) and the 3 main CD-associated CARD15 variants was performed. RESULTS: There was a highly significant increase in IL-22 serum expression in CD patients compared to healthy controls (P = 2.53 x 10(-9)). IL-22 serum levels correlated with disease activity: IL-22 levels in patients with a Crohn's disease activity index (CDAI) >150 were significantly higher than in patients with a CDAI <150 (P = 0.001), while TNF-alpha and IL-6 were not significantly different between these 2 groups. Analyzing the effect of 10 IL23R variants on IL-22 serum levels, we demonstrated that the quotients of mean IL-22 serum levels of carriers of the minor allele to the mean serum IL-22 in wildtype carriers correlated highly with the corresponding CD susceptibility risk for each gene variant (r = 0.807). The IL-22 levels in carriers of CD risk-increasing IL23R variants were significantly higher than in carriers of CD risk-decreasing IL23R variants (P = 0.008). CONCLUSIONS: The Th17 cytokine IL-22 is expressed at high levels in CD and correlates with disease activity, offering a better separation between active and inactive CD than IL-6 and TNF-alpha. IL23R genotypes influence IL-22 serum expression, linking genetic CD susceptibility to Th17 cell function for the first time.     

Persistence of interleukin 7 activity and levels on tumour necrosis factor alpha blockade in patients with rheumatoid arthritis

OBJECTIVES: To identify the mechanism of interleukin (IL)7-stimulated tumour necrosis factor alpha (TNFalpha) production and to determine the relationship between intra-articular IL7 and TNFalpha expression levels in patients with rheumatoid arthritis (RA). In addition, the effect of TNFalpha blockade on IL7 activity and on IL7 levels was studied. METHODS: The effect of IL7 on isolated CD4 T cells and CD14 monocytes/macrophages was studied. IL7 and TNFalpha levels were measured in the synovial fluid of patients with RA. In RA synovial tissue, IL7 and TNFalpha expression was assessed in addition to IL1beta, numbers of inflammatory cells and adhesion molecule expression. The extent to which TNFalpha blockade could prevent IL7-induced lymphocyte responses was studied in vitro. In addition, regulation of serum IL7 levels on anti-TNFalpha therapy (adalimumab) was studied. RESULTS: IL7 induced cell contact-dependent TNFalpha production by cocultures of T cells and monocytes, but not by T cells and monocytes cultured separately. IL7 and TNFalpha levels in RA synovial fluid and synovial tissue significantly correlated. IL7-stimulated lymphocyte responses were not inhibited by TNFalpha blockade. Circulating IL7 levels were significantly reduced in patients who successfully responded to anti-TNFalpha treatment. However, IL7 levels persisted in non-responders. CONCLUSION: The present data suggest that IL7 is an important inducer of T cell-dependent TNFalpha production in RA joints. This may contribute to the correlation of intra-articular IL7 and TNFalpha in these joints. Furthermore, the persistence of IL7-induced inflammatory activity on TNFalpha blockade in vitro and persistence of IL7 levels and disease activity in anti-TNFalpha non-responders suggest that IL7 might additionally promote TNFalpha-independent inflammation.     

Important role of interleukin‐3 in the early phase of collagen‐induced arthritis

Objective

Activation of basophils contributes to memory immune responses and results in exacerbation of collagen‐induced arthritis (CIA). We undertook the present study to analyze the production and biologic effects of interleukin‐3 (IL‐3), a strong activator of basophils, in CIA.

Methods

Arthritis was induced by immunization with type II collagen. Mice were treated with blocking monoclonal antibodies against IL‐3 or with recombinant IL‐3. Clinical scoring, histologic analysis, fluorescence‐activated cell sorter analysis, enzyme‐linked immunosorbent assay, and cell culturing were performed to assess disease activity and IL‐3 production.

Results

IL‐3 was produced in large quantities by collagen‐specific CD4+ T cells in the spleen and was present in the synovial tissue during onset of arthritis, but was down‐regulated in paws with severe inflammation. Blockade of IL‐3 during the time of arthritis onset resulted in profound improvement of the disease, with reductions in synovial leukocyte and cytokine levels, peripheral blood basophil levels, and anticollagen antibody titers. Blockade of IL‐3 during the late phase of arthritis had no beneficial effect. Administration of recombinant IL‐3 during onset of arthritis induced a marked exacerbation of the disease, with increased peripheral blood basophil and plasma IL‐6 levels and increased titers of anticollagen antibody. In studies of the regulation of IL‐3 expression in CD4+ T cells, IL‐6 and IL‐4 suppressed the release of IL‐3 by activated CD4+ T cells, whereas lipopolysaccharide and CpG DNA up‐regulated IL‐3 secretion in activated CD4+ T cells by acting on costimulatory cells.

Conclusion

Taken together, the present results demonstrate for the first time that IL‐3 has an important role in the early phase of CIA.

     

Salivary gland and peripheral blood T helper 1 and 2 cell activity in Sjögren's syndrome compared with non-Sjögren's sicca syndrome

Objectives: To investigate whether differences in T helper (Th) 1 and Th2 cell activity in salivary glands ("local") or ("peripheral") blood can discriminate between Sjögren''s syndrome (SS) and non-Sjögren''s sicca syndrome (nSS-sicca). Additionally, to study relationships of local and peripheral Th cell activities with each other and with disease activity measures. Methods: 62 sicca patients (32 with SS, 30 with nSS-sicca) were studied. Local Th1 (interferon γ (IFNγ)) and Th2 (interleukin (IL) 4) activity were determined using immunohistochemistry. T cell production of IFNγ and IL4 in peripheral blood (PB) was determined by ELISA. Erythrocyte sedimentation rate (ESR) and serum IgG were considered disease activity measures. Results: ESR and serum IgG were higher in patients with SS than in patients with nSS-sicca. Local Th1 cell activity was higher and PB Th1 activity lower in patients with SS than in those with nSS-sicca. Th2 cell activity did not differ significantly between the patient groups. The ratio IFNγ/IL4 was higher in salivary glands and lower in PB in patients with SS than in patients with nSS-sicca. Local and peripheral Th1 and Th2 cell activities correlated with ESR and serum IgG levels. ESR, serum IgG, and local or peripheral Th1 or Th2 cell activity did not discriminate between patients with SS and nSS-sicca. Conclusions: An imbalance between Th1 and Th2 activity in sicca patients is clearly related to the severity of disease, but cannot be used to distinguish between patients with SS and those with nSS-sicca.     

Selective Th2 pattern of cytokine secretion in Mycobacterium avium subsp. paratuberculosis infected Crohn's disease

Background and Aims: The pathogenesis of Crohn's disease (CD) remains unclear. A major controversy has been whether infection with Mycobacterium avium subspecies paratuberculosis (MAP) plays a significant role. Current support for a role of MAP is largely based on epidemiological data. The aim of this study was to determine whether MAP detection in gut biopsies is associated with a different cytokine secretion profile as observed in whole blood culture. Methods: A whole blood culture system was employed to measure cytokine secretion, using an ELISA assay, in subjects with CD (n = 46), ulcerative colitis (n = 30), irritable bowel syndrome (n = 22) and normal controls (n = 18). MAP status was defined by nested PCR using an IS900 sequence unique to MAP. Results: Significantly higher levels of interleukin (IL)‐4 (P < 0.05) and IL‐2 (P < 0.05) were found in MAP+ CD compared to MAP– CD. This was selective, as MAP+ subjects in both normal and disease controls had similar levels of IL‐4 and IL‐2 to those with no detectable MAP. IL‐4 secretion was correlated with IL‐2 production in blood cultures in CD (P < 0.01), consistent with a skewed Th2 immune response. Conclusions: This data set provides the first evidence of altered T cell function linked to MAP infection in CD, and provides a link between detection of MAP and disease. The pattern of cytokine shift in CD is consistent with the concept that the increasing incidence of CD is in part related to the hygiene theory.