Cellular Senescence and SENEX Gene on the Peripheral CD4+CD25+ Treg Cells Enhancement in Elderly

Cellular senescence is a signal transduction process which maintained genomic stability and stopped mammalian cell growth. Furthermore, cellular senescence induces a protective response to a variety of DNA damage. However, this process is also associated with apoptosis, upregulated secretion of inflammatory cytokine, and promoted surrounding tissue damage. When cellular senescence accumulates to a certain extent, it triggers geriatric diseases, such as chronic inflammation, immune senescence-associated tumors and incontrollable infections. Cellular senescence gene SENEX, which was cloned in 2004, has been demonstrated to play a unique gatekeeper function in human endothelial cells when stress-induced pre-mature senescence and apoptosis occurr. The phenomenon that CD4+CD25+ Treg cells accumulated in the aged population has been well studied in recent years. Now Treg accumulation related to immune-pathology has attracted more interest. CD4+CD25+ Treg did not decline and age, but accumulated and suppressed immunoreaction. The enhanced Treg number and function may be associated with stress-induced premature senescence-mediated unique cellular senescence protection mechanisms, and SENEX may play a critical role in this process. In this article, we summarize the cellular senescence and SENEX gene in the accumulation and functional activity of CD4+CD25+ Treg in the elderly.

IL-18和IL-37b对naive CD4^(+)T细胞分化的影响及其在哮喘中的作用研究进展

过敏性哮喘(allergic asthma,AA)是呼吸系统最常见的过敏性疾病之一,CD4^(+)T细胞相关亚型在AA发病中起重要作用。白细胞介素(IL)-18和IL-37b通过与IL-18Rα结合调控naive CD4^(+)T细胞的分化进而在AA中起拮抗作用。鉴于此,了解IL-18和IL-37b在AA naive CD4^(+)T细胞分化中的作用对于AA的病机、诊疗及其相关生物制剂的研发具有重要意义。

Increased CD4/CD8 Lymphocyte ratio predicts favourable neoadjuvant treatment response in gastric cancer:A prospective pilot study

BACKGROUND Despite optimal neoadjuvant chemotherapy only 40%of gastric cancer tumours achieve complete or partial treatment response.In the absence of treatment response,neoadjuvant chemotherapy in gastric cancer contributes to adverse events without additional survival benefit compared to adjuvant treatment or surgery alone.Additional strategies and methods are required to optimize the allocation of existing treatment regimens such as FLOT chemotherapy(5-Fluorouracil,Leucovorin,Oxaliplatin and Docetaxel).Predictive biomarkers detected using immunohistochemistry(IHC)methods may provide useful data regarding treatment response.AIM To investigate the utility of CD4,CD8,Galectin-3 and E-cadherin in predicting neoadjuvant FLOT chemotherapy tumour response in gastric adenocarcinoma.METHODS Forty-three adult patients with gastric adenocarcinoma,of which 18 underwent neoadjuvant chemotherapy,were included in a prospective clinical cohort.Endoscopic biopsies were obtained from gastric cancer and normal adjacent gastric mucosa.Differences in expression of Galectin-3,Ecadherin,CD4^(+)and CD8^(+)molecules between tumours with and without treatment response to neoadjuvant chemotherapy were assessed with IHC.Treatment response was graded by clinical pathologists using the Tumour Regression Score according to the College of American Pathologists criteria.Treatment response was defined as complete or near complete tumour response,whereas partial or poor/no response was defined as incomplete.Digital IHC images were annotated and quantitatively assessed using QuPath 0.3.1.Biomarker expression between responsive and incomplete response tumours was assessed using a two-sided Wilcoxon test.Biomarker expression was also compared between normal and cancer tissue and between 15 paired tumour samples before and after chemotherapy.We performed a preliminary multivariate analysis and power analysis to guide future study.Statistical analyses were completed using R 4.1.2.RESULTS The ratio between CD4^(+)and CD8^(+)lymphocytes was significantly greater in treatment responsive tumours(Wilcoxon,P=0.03).In univariate models,CD4^(+)/CD8^(+)ratio was the only biomarker that significantly predicted favourable treatment response(Accuracy 86%,P<0.001).Using a glmnet multivariate model,high CD4^(+)/CD8^(+)ratio and low Galectin-3 expression were the most influential variables in predicting a favourable treatment response.Analyses of paired samples found that FLOT chemotherapy also results in increased expression of CD4^(+)and CD8^(+)tumour infiltrating lymphocytes(Paired Wilcoxon,P=0.002 and P=0.008,respectively).Our power analysis suggests future study requires at least 35 patients in each treatment response group for CD8 and Galectin-3 molecules,whereas 80 patients in each treatment response group are required to assess CD4 and E-cadherin biomarkers.CONCLUSION We demonstrate that an elevated CD4^(+)/CD8^(+)Ratio is a promising IHC-based biomarker to predict favourable treatment response to FLOT neoadjuvant chemotherapy in locally advanced gastric cancer.

Peripheral CD4^(+)CD8^(+) double positive T cells:A potential marker to evaluate renal impairment susceptibility during systemic lupus erythematosus

Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^(+)CD8^(+)double positive T(DPT) lymphocytes and LN. The study included patients with SLE without renal impairment(SLE-NRI), LN, nephritic syndrome(NS), or nephritis. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Biochemical measurements were performed with peripheral blood in accordance with the recommendations proposed by the National Center for Clinical Laboratories. The proportions of DPT cells in the LN group were significantly higher than that in the SLE-NRI group(t=4.012, P<0.001), NS group(t=3.240,P=0.001), and nephritis group(t=2.57, P=0.011). In the LN group, the risk of renal impairment increased significantly in a DPT cells proportion-dependent manner. The risk of LN was 5.136 times(95% confidence interval, 2.115–12.473) higher in cases with a high proportion of DPT cells than those whose proportion of DPT cells within the normal range. These findings indicated that the proportion of DPT cells could be a potential marker to evaluate LN susceptibility, and the interference of NS and nephritis could be effectively excluded when assessing the risk of renal impairment during SLE with DPT cell proportion.

MBD2 promotes Th2 differentiation in ovalbumin-induced CD4+T cells

Introduction:Allergen-specific CD4+T cells play a central role in autoimmune disorders,allergies and asthma,with Th2-type immunity being the typical functional response of CD4+T cells.This study aimed to investigate the role of MBD2 in regulating Th2 cell differentiation.Methods:Splenic mononuclear cells were extracted from C57BL/6 mice,and CD4+T cells were isolated using magnetic beads and confirmed through flow cytometry.Lentivirus was employed to construct MBD2-silenced CD4+T cells.In vitro experiments were performed to treat splenogenic mononuclear cells and CD4+T cells with Ovalbumin(OVA),and Th2 cell ratios and IL-4 levels were assessed using flow cytometry and ELISA.Results:The purity of the isolated CD4+T cells was 95.73%,confirming successful isolation of primary CD4+T cells.Compared to the control group,the Th2 cell ratio exhibited an increase in the Th2-induced group.Treatment with 5-Aza(concentrations,1-100μM)promoted Th2 cell differentiation and increased IL-4 levels.Notably,when combined with Th2 induction and 10μM 5-Aza treatment,silencing MBD2 further amplified Th2 cell ratios and elevated IL-4 levels in cell supernatants.Furthermore,OVA(concentration,200μg/mL)induced the differentiation of CD4+T cells into Th2 cells and increased IL-4 secretion.Interestingly,silencing MBD2 significantly increased the Th2 cell ratio and IL-4 levels in OVA-treated CD4+T cells.Conclusion:In summary,OVA promoted CD4+T cell differentiation into Th2 cells and enhanced IL-4 levels.MBD2 was identified as a mediator of Th2 cell differentiation in splenic-derived CD4+T cells,influenced by OVA or 5-Aza treatment.

Combined TIM-3 and PD-1 blockade restrains hepatocellular carcinoma development by facilitating CD4+ and CD8+T cellmediated antitumor immune responses

BACKGROUND Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)are beneficial to the resumption of anti-tumor immunity response and hold extreme potential as efficient therapies for certain malignancies.However,ICIs with a single target exhibit poor overall response rate in hepatocellular carcinoma(HCC)patients due to the complex pathological mechanisms of HCC.AIM To investigate the effects of combined TIM-3 and PD-1 blockade on tumor development in an HCC mouse model,aiming to identify more effective immunotherapies and provide more treatment options for HCC patients.METHODS The levels of PD-1 and TIM-3 on CD4+and CD8+T cells from tumor tissues,ascites,and matched adjacent tissues from HCC patients were determined with flow cytometry.An HCC xenograft mouse model was established and treated with anti-TIM-3 monoclonal antibody(mAb)and/or anti-PD-1 mAb.Tumor growth in each group was measured.Hematoxylin and eosin staining and immunohistochemical staining were used to evaluate T cell infiltration in tumors.The percentage of CD4+and CD8+T cells in tissue samples from mice was tested with flow cytometry.The percentages of PD-1+CD8+,TIM-3+CD8+,and PD-1+TIM-3+CD8+T cells was accessed by flow cytometry.The levels of the cytokines including tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),interleukin(IL)-6,and IL-10 in tumor tissues were gauged with enzyme-linked immunosorbent assay kits.RESULTS We confirmed that PD-1 and TIM-3 expression was substantially upregulated in CD4+and CD8+T cells isolated from tumor tissues and ascites of HCC patients.TIM-3 mAb and PD-1 mAb treatment both reduced tumor volume and weight,while combined blockade had more substantial anti-tumor effects than individual treatment.Then we showed that combined therapy increased T cell infiltration into tumor tissues,and downregulated PD-1 and TIM-3 expression on CD8+T cells in tumor tissues.Moreover,combined treatment facilitated the production of T cell effector cytokines TNF-α and IFN-γ,and reduced the production of immunosuppressive cytokines IL-10 and IL-6 in tumor tissues.Thus,we implicated that combined blockade could ameliorate T cell exhaustion in HCC mouse model.CONCLUSION Combined TIM-3 and PD-1 blockade restrains HCC development by facilitating CD4+ and CD8+T cell-mediated antitumor immune responses.

Nocardia cyriacigeorgica infection in a patient with repeated fever and CD4+T cell deficiency:A case report

BACKGROUND Nocardia pneumonia shares similar imaging and clinical features with pulmonary tuberculosis and lung neoplasms,but the treatment and anti-infective medication are completely different.Here,we report a case of pulmonary nocardiosis caused by Nocardia cyriacigeorgica(N.cyriacigeorgica),which was misdiagnosed as community-acquired pneumonia(CAP)with repeated fever.CASE SUMMARY A 55-year-old female was diagnosed with community-acquired pneumonia in the local hospital because of repeated fever and chest pain for two months.After the anti-infection treatment failed in the local hospital,the patient came to our hospital for further treatment.Enhanced computed tomography showed multiple patchy,nodular and strip-shaped high-density shadows in both lungs.A routine haematological examination was performed and showed abnormalities in CD19+B cells and CD4+T cells.Positive acid-fast bifurcating filaments and branching gram-positive rods were observed in the bronchoalveolar lavage fluid of the patient under an oil microscope,which was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry as N.cyriacigeorgica.The patient’s condition quickly improved after taking 0.96 g compound sulfamethoxazole tablets three times a day.CONCLUSION The antibiotic treatment of Nocardia pneumonia is different from that of common CAP.Attention should be given to the pathogenic examination results of patients with recurrent fever.Nocardia pneumonia is an opportunistic infection.Patients with CD4+T-cell deficiency should be aware of Nocardia infection.

HIV-1 RNA Viral Load, CD4 Count and Some Haematological Parameters of People Living with HIV in the Enugu Metropolis

Background: It is widely known that the human immune-deficiency virus (HIV) induces biochemical and physiological changes in affected persons. Consequently, the overall aim of this study was to evaluate the HIV-1 RNA viral load, CD4 count, and certain haematological parameters among HIV treatment-na?ve subjects in the Enugu metropolis of Nigeria. Materials and Methods: A total of 252 HIV-infected, ART-native subjects (≥18) attending the University of Nigeria Teaching Hospital (UNTH) in Ituku-Ozalla, Enugu were recruited for this study and were made up of 157 (62.3%) females and 95 (37.7%) males. A total of 250 HIV-negative subjects were used as control subjects (100 males and 150 females). Blood samples were collected from all the participants and their HIV-1 status was confirmed by an immunoblot confirmatory test. Their haematological parameters and CD4 count were evaluated, while the HIV-1 viral load was only assessed on confirmed HIV-positive subjects. Results: There was female predominance (62.3%) among these HIV-positive subjects. The mean age of HIV-positive subjects was 39.16 ± 10.08 years while the mean age of the control subjects was 34.8 ± 8.6 years. The age group of 31 - 40 years (102/252 (40.5%)) constituted most of the test subjects. The total white blood cells (TWBC) (6.05 ± 5.46), lymphocyte counts (36 ± 14), haemoglobin concentrations (Hb) (9.85 ± 7.36) and the CD4 counts (242 ± 228) of the HIV-infected subjects showed a significant difference when compared with their control counterpart values of TWBC (4.5 ± 0.568), lymphocytes (39.67 ± 8.2), Hb (13.48 ± 1.5), and CD4 counts (807 ± 249) (p 0.05). Anaemia, lymphocytopenia, and thrombocytopenia were the haematological abnormalities seen in the HIV-positive subjects. HIV viral load correlated with haemoglobin concentration, CD4 count, lymphocyte count, and neutrophil count (p Conclusion: Prognostic factors, such as haemoglobin concentrations, CD4 counts, lymphocyte counts, and neutrophil counts can be used to monitor patients’ viral loads since they correlate with the latter;furthermore, age is a factor that should be considered in the management of HIV-positive patients.

Levels of v5 and v6 CD44 splice variants in serum of patients with colorectal cancer are not correlated with pT stage,histopathological grade of malignancy and clinical features

AIM:This study was designed to compare the levels of v5 and v6 splice variants of CD44 evaluated using EITSA test in the serum of patients with colorectal cancer in different stages of progression of the disease estimated in pT stage according to WHO score,histopathological grade of malignancy and some clinicopathological features. METHODS:The serum obtained from 114 persons with colorectal adenocarcinomas was examined using ELISA method,pT stage and grade of malignancy of the tumour were examined in formalin fixed and paraffin embedded materials obtained during operation. RESULTS:Only the level of CD44 v5 in the serum of patients before operation with G2 pT4 tumour was lower than that in other probes and the difference was statistically significant. We did not find any other correlations between the level of v5 and v6 CD44 variants and other evaluated parameters. CONCLUSION:The level of CD44 v5 and v6 estimated by ELISA test in the serum can not be used as a prognostic factor in colorectal cancer.

CD3^+ CD4^+ T细胞计数在重型再生障碍性贫血患者异基因造血干细胞移植术后病毒感染的预示价值

目的:探讨重型再生障碍性贫血(SAA)患者在异基因造血干细胞移植(allo-HSCT)后CD3^+ CD4^+ T细胞对预测病毒感染的价值。方法:选广州市第一人民医院血液内科2014年1月至2016年5月SAA行allo-HSCT患者78例。用流式细胞术检测移植后第1、2、3、6、12个月外周血CD3^+ CD4^+ T细胞计数,并根据结果分为<50/μl(n=120)、50-100/μl(n=48)和>100/μl 3个组(n=123)。在时间点的前后2周,监测巨细胞病毒、EB病毒DNA的感染情况,计算各类感染发生率。移植后3个月,按移植患者的CD3^+ CD4^+ T细胞计数分为2组,>100/μl组(n=30)及≤100/μl组(n=48),计算2组的CMV和EBV感染率、持续时间及发病情况,并进行随访,行生存情况比较。结果:CD3^+ CD4^+ T细胞计数>100/μl组较50-100/μl和<50/μl组的CMV、EBV感染率下降。移植后第3个月,CD3^+ CD4^+ T细胞计数>100/μl组CMV及EBV感染率较≤100/μl组低,CMV感染持续时间缩短;移植后3月,CD3^+ CD4^+ T细胞绝对数>100/μl组生存情况优于≤100/μl组。结论:SAA患者allo-HSCT后,CD3^+ CD4^+ T细胞数恢复至100/μl以上时,CMV及EBV感染率明显下降。移植后第3个月,CD3^+ CD4^+ T细胞绝对数>100/μl时CMV及EBV感染率明显下降,CMV感染持续时间缩短,生存率较高。CD3^+ CD4^+ T细胞绝对数是SAA患者alloHSCT后良好的CMV及EBV感染的一个预示指标。

黑色素瘤B16细胞通过释放外泌体诱导naïve CD4^(+) T细胞分化为Treg

目的检测小鼠黑色素瘤细胞B16通过释放外泌体诱导naïve CD4^(+)T细胞分化为调节性T细胞(regulatory T cell,Treg)的能力。方法通过试剂盒和超速离心获得B16培养上清中的外泌体,用透射电镜观察外泌体形态,Western blot检测外泌体标记性蛋白的表达水平,通过Transwell共培养验证外泌体或B16细胞对naïve CD4^(+)T细胞诱导分化的能力,流式细胞术检测小鼠脾脏、肿瘤内Th17、Treg细胞的频率,qPCR检测T细胞亚群特异性转录因子、炎症因子的mRNA水平。结果B16细胞外泌体的直径为30~100 nm,呈圆形碟状结构,外泌体高表达Tsg101、HSP60和Alix,低表达GAPDH;在体外,B16细胞外泌体可直接诱导naïve CD4^(+)T细胞分化成Treg,但不能诱导其分化为Th17;小鼠在体实验证实,B16细胞外泌体能够诱导Treg细胞并聚集于小鼠脾脏中,同时能够增加B16瘤体内Treg细胞的数量,并活化使其表达更高水平的IL-10、TGF-β和Foxp3。结论B16细胞外泌体通过诱导naïve CD4^(+)T细胞分化为Treg,并将其募集至肿瘤组织,从而维持肿瘤的免疫抑制微环境。

Changes of CD4^+CD25^+ Regulatory T Cells in Patients with Acute Coronary Syndrome and the Effects of Atorvastatin

The function of CD4＋CD25＋ regulatory T lymphocytes （Treg） in patients with acute coronary syndrome （ACS） and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups： group C receiving conventional therapy （n=24）, and group C＋A receiving conventional therapy＋atorvastatin （10 mg/day, n=24）. T lymphocytes from ACS patients （before and 2 weeks after the treatment） or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction （MLR）. ELISA was used to measure the serum levels of cytokines （IL-10, TGF-β1 and IFN-γ） before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly （P〈0.01）, the inhibitory ability of Treg on the T lymphocytes proliferation was reduced （P〈0.01）, IFN-γ levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients. After treatment with atorvastatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were significantly increased in ACS patients. Serum IFN-γ was decreased significantly, while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1, but negatively with serum IFN-γ and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restoration of immune homeostasis.

Foxp3^+ CD4^+调节性T细胞在急性期和慢性期大棚作业农民肺外周血中的变化及其意义

目的观察急性期和慢性期大棚作业农民肺(简称大棚肺,greenhouse farmer's lung,GFLD)患者和大棚作业健康农民外周血中Foxp3+CD4+调节性T细胞(regulatory T cells,Treg细胞)、CD4+CD25+双阳性T细胞比例和外周血T细胞亚群的变化,探讨Foxp3+CD4+Treg细胞在两个不同时期GFLD发病中的调节性作用。方法①该院呼吸内科于2006年8月～2009年6月采用分层、随机和整群抽样方法,对辽宁省沈阳市、锦州市和朝阳市3个地区进行GFLD流行病学调查,应调查5 880人,有效调查5 420人,应答率92.2%,共调查菌棚167个,家禽棚126个,花卉棚208个,蔬菜棚334个,共835个;其中沈阳市的蔬菜棚231个,蔬菜棚从业农民共855人,筛查出GFLD患者55例,排除不符合本研究纳入标准的患者13例,最终纳入本研究的GFLD患者42例,男27例,女15例,对其进行肺部HRCT检查;按照GFLD的不同分期将急性期GFLD患者20例设为急性期组、慢性期GFLD患者22例设为慢性期组(吸烟者和亚急性期GFLD患者排除),选取同期同村大棚从业健康农民17例设为对照组。②各组受试者统一于清晨8时抽取空腹静脉血2 mL,严格按照试剂盒所提示的方法处理标本,处理标本后1 h内应用流式细胞仪检测受试者外周血的Foxp3+CD4+Treg细胞比例和T淋巴细胞亚群。多组间比较采用单因素方差分析,多组内两两比较采用SNK检验(方差齐)和Games-Howell法(方差不齐);Treg细胞与T细胞亚群关系用Spearman相关分析进行相关性检验。结果①急性期组和慢性期组外周血Foxp3+CD4+Treg细胞比例[(0.43±0.17)%]和[(1.10±0.26)%]明显少于对照组[(1.79±0.60)%],差异有显著性(F=62.68,P<0.01);②急性期组和慢性期组外周血CD4和CD25双阳性细胞比例[(2.70±1.04)%]和[(2.98±1.35)%]明显低于对照组[(4.72±1.65)%],与对照组相比,差异有显著性(F=11.82,P<0.01);急性期组和慢性期组比较,外周血CD4和CD25双阳性细胞比例差异无显著性(P>0.05);③急性期组和慢性期组外周血中CD4+CD3+%比例(19.79±10.96)%和(30.96±10.76)%较对照组(36.86±11.57)%明显减少,尤以急性期组减少为著,差异均有显著性(F=11.54,P<0.01);急性期组和慢性期组外周血中CD8+CD3+%比例(36.65±18.71)%和(21.87±7.53)%较对照组(20.15±6.14)%明显增加,而急性期组增加的更为显著,差异有显著性(F=10.66,P<0.01)。与对照组相比,急性期组和慢性期组外周血CD4+/CD8+的比值(0.56±0.18)和(1.43±0.21)明显降低,三组比较均差异有显著性(F=214.09,P<0.05);④相关性分析:急性期组和慢性期组外周血中CD4+/CD8+比值与其外周血中Foxp3+CD4+Treg细胞比例和CD4和CD25双阳性细胞的比例均呈显著正相关(r值分别为0.827和0.420,均P<0.05);急性期组和慢性期组外周血Foxp3+CD4+Treg细胞比例和CD4+/CD8+比值与年龄之间均无相关性(r值分别为0.079和0.131,P>0.05)。结论 GFLD患者体内Foxp3+CD4+Treg细胞的下调或过度消耗可能是GFLD发病机制中的重要因素之一。

CD45RB^(high) CD4^+幼稚T细胞诱导严重联合免疫缺陷型小鼠慢性结肠炎模型的建立

目的:建立CD45RBhighCD4+幼稚T细胞诱导严重联合免疫缺陷型(SCID)小鼠慢性结肠炎模型,并探讨该结肠炎模型的免疫病理特征。方法:采用流式细胞仪分离BALB/c小鼠(H-2d基因表型)脾脏CD45RBhighCD4+幼稚T细胞,经尾静脉或腹腔注射植入21只同基因型SCID小鼠体内,观察慢性结肠炎的发生。8周后处死SCID小鼠,分离结肠黏膜固有层内CD4+T淋巴细胞,体外刺激,分别采用ELISA法和RT-PCR法检测炎症结肠黏膜组织内炎症细胞因子(IFN-γ、IL-2、IL-4、IL-5、TNF-α)及其mRNA的表达水平。以16只正常BALB/c小鼠作对照。结果:CD45RBhighCD4+幼稚T细胞植入SCID小鼠(4.1±0.3)周后,小鼠体重开始下降,大便变软;(7.4±0.6)周后出现腹泻、体重明显下降、脱肛等慢性结肠炎症状;组织病理检查发现结肠黏膜层、黏膜下层、肌层及浆膜层有大量的淋巴细胞浸润,以黏膜层和黏膜下层明显,并出现肠上皮细胞炎性增生、黏膜溃疡形成。与正常BALB/c小鼠比较,CD45RBhighCD4+幼稚T细胞诱导后,SCID小鼠结肠黏膜固有层CD4+T细胞IFN-γ、IL-2、TNF-α分泌水平增高(P<0.005),结肠黏膜组织内IL-2、IFN-γ、TNF-αmRNA水平亦升高(P<0.005)。结论:CD45RBhighCD4+幼稚T细胞可诱导SCID小鼠发生慢性结肠炎。

The human leucocyte differentiation antigens (HLDA) workshops: the evolv-ing role of antibodies in research, diagnosis and therapy

The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved （including an estimate of the number of leucocyte surface molecules still to be discovered）, and how the field can best move forward.

All-transRetinoic Acid Regulates Th1/Th2 Balance in CD4+T cells When GATA-3 is Deficient

The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balance under a strong Thl-polarizing condition. Therefore, the purpose of our study was to examine the effect of vitamin A metabolite allotrans retinoic acid （ATRA） on ThloTh2 differentiation in CD4~ T cells under GATA-3 deficiency, which can induce Thl-polarizing condition. In the present study, GATA-3 deficiency T cells were induced by siRNA and checked by real-time quantitative PCR and western blot. GATA-3 deficiency CD4＋ T cells and normal CD4＋ T were treated for 48 h with or without ATRA.

Expression of CD40 and CD40L on Peripheral Blood Mononuclear Cells in Patients with Condyloma Acuminatum

To observe the expression of CD40/CD40L on peripheral blood mononuclear cells （PBMC） in patients with eondyloma aeuminatum （CA）, flow eytometry was employed to examine the expression of CD40 and CD40L on PMBC in 36 patients with CA and 20 healthy controls. Our results showed that mean level of CD40 expression in CA patients was significantly lower than that in the controls （6.58 %±2.74 % vs 14.81 %±6.12 %, t=5. 703, P〈0.05）; the average level of CD40L in CA patients was also significantly lower than that in the controls （0.73 % ±0.54 % vs 2.67 %±2.43 %, t=3. 532, P〈0.05）. Our resutls suggest that the reduced costimulatory interaction of CD40 and CD40L in CA patients may be one of the important factors responsible for the low cellular immunity.

Construction of cell lines with CD44 cDNA and its application in hepatocellular carcinoma

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外周血白细胞介素-17 CD4^+CD25^+调节性T细胞白三烯B4变化与患儿支气管哮喘活动状态的关系研究

支气管哮喘是儿童时期最常见的慢性气道疾病,20余年来我国儿童哮喘的患病率呈明显上升趋势,严重危害儿童健康,全国14岁以下儿童哮喘的累积患病率2010年为3.02%,但其发病机制目前尚不完全清楚。慢性气道炎症是支气管哮喘的本质,传统观点认为,

The effect of ABV regimen on CD4 lymphocyte count in patients with advanced HIV related Kaposi’s sarcoma

Objective: The combination of highly active antiretroviral therapy (HAART) and chemotherapy with ABV regimen (doxorubicin, bleomycin and vincristine) is a promising approach for the treatment of advanced HIV-related Kaposi's sarcoma (KS). Here we analyzed the relationship between the CD4 lymphocyte cell count and the clinical response to chemotherapy. Methods: The 176 HIV infected patients with advanced KS who failed to respond to prior HAART were selected. All these patients were then preceded to chemotherapy with ABV regimen which was administered at 3 weekly intervals for 6 cycles. For each patient CD4 cell count was done before starting chemotherapy and after finishing 6 cycles of chemotherapy. The difference of CD4 cell counts pre chemotherapy and post chemotherapy was compared with the clinical progress of the patients after 6 cycles of chemotherapy. Results: The overall clinical remission was shown in 93.7% patients. Progressive disease (PD) and no change in clinical condition (NC) was shown in 6.3% patients. The increase in CD4 cell count post chemotherapy was found in 89.8% patients and the decrease in CD4 cell count was seen in 10.2% patients. The difference of the mean CD4 cell counts for patients in group CR + PR (complete relief + partial relief) before and after chemotherapy was highly significant. The difference of the mean CD4 cell counts for patients in group NC + PD before and after chemotherapy was not significant. The difference in CD4 cell counts in CR + PR and NC + PD groups before and after chemotherapy was highly significant. Conclusion: The HIV related KS patients on HAART benefit from the chemotherapy as it increases the CD4 cell count and it has positive impact on clinical remission of KS.