Elevated Th22 as well as Th17 cells associated with therapeutic outcome and clinical stage are potential targets in patients with multiple myeloma

T helper (Th) cell imbalance plays important roles in tumor development and their effects in Multiple myeloma (MM) remain unclear. In the present study, we investigated the levels and clinical significance of Th22, Th17 and Th1 cells in patients with MM. Th subsets were examined by flow cytometry. Plasma IL-22, IL-17A and IFN-γ concentrations were measured by ELISA. AHR and RORC mRNA expression was examined by RT-PCR. Here, we found that the frequency of Th22 cells was significantly elevated in peripheral blood (PB) and bone marrow (BM) of newly-diagnosed MM patients, and recovered in complete remission patients after chemotherapy. The circulating Th17 cells accompanied by IL-17A levels were also up-regulated in MM patients and decreased after remission. We also found that there was a significantly positive correlation between Th22 and Th17 cells in MM patients. Moreover, the frequencies of Th22 and Th17 cells were higher in stage III than in stage I+II of MM. Our data demonstrated that Th22 and Th17 cells might be important therapeutic targets in multiple myeloma and could facilitate the effect of antitumor immunotherapy.     

Effects of interferon-alpha-2a on Th3 cytokine response in multiple myeloma patients

AIMS AND BACKGROUND: Multiple myeloma cells increase Th3 cytokine response by secreting TGF-beta, which causes defective Th1 and Th2 cytokine responses. Therefore, a significant suppression of the immune system is seen in multiple myeloma. Interferon-alpha (IFN-alpha) is used in the treatment of multiple myeloma due to its immunomodulatory and anti-tumoral effects. We attempted to define the characteristics of immune cytokine responses and the effects of IFN-alpha-2a on the immune response in multiple myeloma. METHODS: Fifteen patients with multiple myeloma and 15 healthy controls were enrolled. IFN-alpha-2a, 3 million units/day x 3 times/week, was administered subcutaneously to the patients for 2 weeks. Cytokines (TGF-beta, IL-1, IL-2, IL-4, IL-10, IFN-gamma) were assessed by the ELISA method in sera of the patients in pretreatment and posttreatment periods and in the sera of the controls. RESULTS: IL-2 and IL-4 levels in patients, before IFN-alpha-2a, were lower than the controls, whereas TGF-beta levels were higher than the controls. In other words, Th3 cytokine response was increased and Th1 and Th2 cytokine responses were decreased in patients. A short course of IFN-alpha-2a increased IL-2 levels. CONCLUSIONS: These findings suggest IFN-alpha-2a may enhance nonTh3 cytokine responses in multiple myeloma patients.     

胃癌患者化疗前后Th1/Th2细胞因子的检测及其临床意义

目的 研究胃癌患者化疗前后CD4+T淋巴细胞中Th1、Th2类细胞因子的表达水平和Th1/Th2值的变化及其临床意义.方法 60例胃癌患者接受FOLFOX4方案化疗,应用流式细胞仪对化疗前后患者外周血特异性细胞因子的表达变化进行分析.结果 化疗后,全组胃癌患者外周血CD4+T淋巴细胞分泌的γ干扰素(IFN-γ)的表达水平为11.4%±5.0%,较化疗前升高(P＜0.05);白介素10(IL-10)的表达水平为3.6%±1.2%,较化疗前降低(P＜0.05);Th1/Th2(IFN-γ/IL-4)的值为3.4±1.0,与化疗前比较,无明显变化(P＞0.05).15例化疗后疗效为部分缓解的患者,外周血CD4+T淋巴细胞分泌的IFN-γ和肿瘤坏死因子-α(TNF-α)的表达水平分别为14.8%±8.0%和5.9%±2.0%,均较化疗前升高(均P＜0.05);Th1/Th2(IFN-γ/IL-4)的值为4.0±1.5,明显高于化疗前水平(P＜0.01).结论 有效的化疗可减轻患者机体的肿瘤负荷,降低Th1类细胞因子向Th2类细胞因子漂移的程度;但胃癌化疗的有效率较低,因此对胃癌化疗者,改善机体免疫功能仍是很重要的治疗措施.     

Prognostic impact of tumour-infiltrating Th2 and regulatory T cells in classical Hodgkin lymphoma

Classical Hodgkin Lymphoma (cHL) is morphologically characterized by a small number of tumour cells, Hodgkin and Reed-Sternberg (HRS) cells, surrounded by numerous tumour-infiltrating lymphocytes (TIL). The functional role of these TIL is still controversial. While generally considered to represent an anti-tumour immune response, TIL in cHL might result from the profoundly deregulated immunity of cHL patients. Eighty-seven cases of cHL were available to evaluate the prognostical significance of tumour-infiltrating cytotoxic T lymphocytes (CTL), T helper 1 (Th1) cells, T helper 2 (Th2) cells and regulatory T cells (Treg). We confirm that in cHL the microenvironment is dominated by Th2 cells and Treg and show that large numbers of Th2 cells are associated with significantly improved disease-free survival (p = 0.021) and event-free survival (p = 0.012). Furthermore, a high ratio of Treg over Th2 cells resulted in a significantly shortened disease-free survival (p = 0.025). These observations suggest that Treg may exert inhibitory effects on anti-tumour immune responses mediated through Th2 cells and that Th2 cells may be more important for effective anti-tumour immunity than anticipated.     

Roles of idiotype-specific t cells in myeloma cell growth and survival: Th1 and CTL cells are tumoricidal while Th2 cells promote tumor growth

Idiotype (Id) protein, secreted by myeloma cells, is a tumor-specific antigen. Id-based immunotherapy has been explored in patients with myeloma, and results were disappointing. Although previous studies have shown that Id-specific CTLs are able to lyse myeloma cells, it is unclear whether other types of Id-specific T cells, such as type-1 T-helper (Th1) and type-2 T-helper (Th2) cells, are also able to suppress or kill myeloma cells. Using a 5T murine myeloma model, we generated T-cell clones of different subsets and examined their function in the context of myeloma cells. Id-specific CTLs specifically lysed myeloma cells via MHC class I, perforin, and Fas ligand (FasL), and Th1, but not Th2, cells lysed the myeloma cells by FasL-Fas interaction. CTL and Th1 cells also suppressed the growth and function of myeloma cells, whereas Th2 cells promoted the proliferation and enhanced the secretion of Id protein and cytokines by myeloma cells. CTL and Th1, but not Th2, cells were able to eradicate established myeloma in vivo after adoptive transfer. These results show that Id-specific CTL and Th1 are promising effector cells, whereas Th2 provide no protection and may even promote tumor progression in vivo.     

Th/Tr淋巴细胞比值评估乳腺癌患者抗肿瘤免疫状态

目的：探讨用Th/Tr淋巴细胞比值评估乳腺癌患者的抗肿瘤免疫状态。方法：采用流式细胞术检测53例不同分期的乳腺癌患者化疗前外周血中CD4^＋Th细胞、CD4^＋CD25^＋Tr细胞水平,计算Th/Tr比值,并与30例健康志愿者进行比较。结果：有转移与无转移的乳腺癌患者Tr细胞绝对值差异无统计学意义（103±75vs 109±70,P=0.722）。有转移的乳腺癌患者Th/Tr淋巴细胞比值小于无转移者（3.83±1.37 vs 6.11±2.93,P〈0.001）,无转移患者小于健康志愿者（6.11±2.93 vs 11.24±1.84,P〈0.001）。结论：Th/Tr比值对乳腺癌患者抗肿瘤免疫状态的评估优于Tr细胞计数,Th/Tr比值在乳腺癌患者尤其是有转移的乳腺癌患者中显著降低,其水平变化可作为评估乳腺癌患者免疫状态的有效指标。     

自体肿瘤瘤苗对荷瘤鼠Th1、Th2型细胞因子及细胞毒作用的影响

目的研究经处理的H22肝癌细胞肿瘤瘤苗作为全细胞瘤苗对H22荷瘤小鼠体内Th1/Th2细胞比例和细胞因子的影响以及CTL的杀伤活性.方法用加重组白细胞介素2、重组粒细胞单核细胞集落刺激因子及福氏不完全佐剂制成疫苗,建立荷瘤小鼠模型,用51Cr释放法测定瘤苗免疫组、荷瘤组、正常组小鼠脾细胞对亲本H22肝癌细胞的杀伤活性;流式细胞仪检测单个核细胞中的Th1和Th2细胞,并取血检测血清中IL-10、IFN-γ水平.结果效靶比为200:1时,免疫小鼠脾细胞体外杀伤亲本H22肝癌细胞的杀伤率为38.3%,显著高于荷瘤组的13.6%,正常组的7.5%,以及对S180细胞的9.1%(P均＜0.05).瘤苗免疫组Th1细胞及Th1/Th2细胞的比值显著升高(P＜0.01),血清IFN-γ较对照组明显升高(P＜0.01);血清IL-10较对照组明显降低(P＜0.01).结论肿瘤细胞加小剂量IL-2和GM-CSF及佐剂组成的肿瘤细胞瘤苗可激发特异性细胞介导的免疫反应,改善抗肿瘤免疫反应.     

Th1/Th2偏移与肿瘤免疫研究进展

Th1/Th2平衡是维持机体正常免疫状态的重要因素,其失衡参与许多疾病。近年来关于Th1/Th2漂移与恶性肿瘤的关系已成为研究的重点。设法逆转Th1/Th2漂移方向,增强Th1免疫,将成为肿瘤免疫治疗的新方法。     

Systemic and Tumor Th1 and Th2 Inflammatory Profile and Macrophages in Lung Cancer: Influence of Underlying Chronic Respiratory Disease

IntroductionChronic respiratory conditions, especially chronic obstructive pulmonary disease (COPD), and inflammatory events underlie lung cancer (LC). We hypothesized that profiles of T helper 1 and T helper 2 cytokines and type 1 and type 2 macrophages (M1 and M2) are differentially expressed in lung tumors and blood of patients with NSCLC with and without COPD and that the ratio M1/M2 specifically may influence their survival.MethodsIn blood, inflammatory cytokines (determined by enzyme-linked immunosorbent assay) were quantified in 80 patients with LC (60 with LC and COPD [the LC-COPD group] and 20 with LC only [the LC-only group]) and lung specimens (tumor and nontumor) from those undergoing thoracotomy (20 in the LC-COPD group and 20 in the LC-only group).ResultsIn the LC-COPD group compared with in the LC-only group, systemic levels of tumor necrosis factor-α, interleukin-2 (IL-2), transforming growth factor-β, and IL-10 were increased, whereas vascular endothelial growth factor and IL-4 levels were decreased. In lung tumors, levels of tumor necrosis factor-α, transforming growth factor-β, and IL-10 were higher than in nontumor parenchyma in the LC-COPD group, whereas IL-2 and vascular endothelial growth factor levels were higher in tumors of both the LC-only and LC-COPD groups. Compared with in nontumor lung, M1 macrophage counts were reduced whereas M2 counts were increased in tumors of both patient groups, and the M1/M2 ratio was higher in the LC-COPD group than the LC-only group. M1 and M2 counts did not influence patients’ survival.ConclusionsThe relative predominance of T helper 1 cytokines and M1 macrophages in the blood and tumors of patients with underlying COPD imply that a stronger proinflammatory pattern exists in these patients. Inflammation should not be targeted systematically in all patients with LC. Screening for the presence of underlying respiratory diseases and identification of the specific inflammatory pattern should be carried out in patients with LC, at least in early stages of their disease.     

利妥昔单抗对弥漫大B细胞淋巴瘤患者Th17细胞及相关细胞因子影响的体外实验

目的 探讨利妥昔单抗对弥漫大B细胞淋巴瘤(DLBCL)患者Th17细胞及相关细胞因子体外的影响及其意义.方法 DLBCL初治患者(DLBCL组)20例和健康对照者(健康对照组)20名,每个对象分别采集4份外周血标本,分离外周血单个核细胞(PBMC),按照培养条件的不同分成4个亚组:空白组(A亚组)、加入利妥昔单抗组(B亚组)、加入利妥昔单抗和血清组(C亚组)和极化组(D亚组)[加白细胞介素6(IL-6)和转化生长因子(TGF-β)].培养后分别采用流式细胞术检测各亚组外周血PBMC中Th17细胞比例,酶联免疫吸附法(ELISA)检测上述培养液中白细胞介素17(IL-17)的表达水平.结果 健康对照组中,D亚组的Th17细胞比例和IL-17水平分别为(17.12±4.90)％、(45.735±10.012)pg/ml,均高于A、B、C亚组(P＜0.05),A、B、C亚组之间比较差异均无统计学意义(P＞0.05).DLBCL组A亚组的Th17细胞比例及IL-17水平为(0.69±0.24)％、(6.012±1.312)pg/ml,均低于健康对照组A亚组的(2.43±0.61)％、(8.217± 1.681)pg/ml(P＜ 0.05);在与利妥昔单抗一起体外培养后,DLBCL组中B、C和D亚组的Th17细胞比例分别为(2.34±0.48)％、(2.31±0.53)％和(16.92±4.81)％,IL-17水平分别为(7.944±1.538) pg/ml、(7.957±1.533) pg/ml和(44.417±9.881) pg/ml,均高于A亚组,且D亚组明显高于B、C亚组(P＜0.05).B、C亚组之间比较差异无统计学意义(P＞0.05).结论 体外实验证实,DLBCL患者外周血PBMC中Th17细胞比例低于健康人,利妥昔单抗作用于DLBCL患者外周血PBMC后可升高Th17细胞比例.     

大肠癌患者外周血Th1/Th2的检测及其临床意义

目的 检测大肠癌患者外周血CD+4细胞Th1、Th2细胞因子的表达水平,观察大肠癌患者Th1/Th2漂移的幅度,探讨Th1、Th2细胞因子与大肠癌发生、发展的关系.方法 采取实验对象的清晨空腹静脉血标本,用Th1、Th2细胞因子标记流式细胞技术检测Th1类细胞因子IFN-γ,Th2类细胞因子IL-4,计算Th1/Th2(IFNγ/IL-4),进行统计学分析.结果 大肠癌患者IFN-γ的表达率为(11.7±1.86)%,健康对照组IFN-γ的表达率为(16.4±6.07)%,大肠癌组比健康对照组明显减低,差异有统计学意义(P＜0.05).大肠癌患者IL-4的表达率为(2.8±0.32)%,健康对照组IL-4的表达率为(1.8±0.19)%,大肠癌组比健康对照组升高,差异有统计学意义(P＜0.05).大肠癌患者外周血IFN-γ/IL-4为4.2±0.94,健康对照组外周血IFN-γ/IL-4为9.7±1.11,差异有统计学意义(P＜0.05).结论 大肠癌患者外周血CD+4细胞表达Th2型细胞因子占优势,Th1/Th2平衡失调,向Th2方向漂移,导致机体免疫功能低下,是大肠癌复发或转移的原因之一.     

软骨肉瘤患者Th1/Th2的变化

目的观察软骨肉瘤患者T淋巴细胞亚群中Th1/Th2的变化,为细胞因子免疫治疗提供依据。方法应用放射免疫分析法以及酶联免疫分析法检测32例软骨肉瘤患者血清中IL-2、IL-4、IL-6、IL-10、IL-12的含量,检测外周血单个核细胞在有或无植物血凝素(PHA)存在情况下培养上清中IL-2、IL-4含量。结果软骨肉瘤患者血清及培养上清中IL-2、IL-12减少(P＜0.001),而IL-10、IL-4、IL-6含量增加(P＜0.01),在使用PHA刺激时,患者淋巴细胞分泌IL-2能力显著降低,而IL-4显著升高。结论软骨肉瘤患者体内存在有Th1/Th2平衡失调,其中Th1亚群功能抑制,Th2亚群功能亢进。     

激动性CD40抗体通过调节Th1/Th2平衡增强抗肿瘤作用的机制研究

  目的  探讨激动性CD40抗体中单链抗体（CD40ScFv）和单克隆抗体（CD40mAb）抑制小鼠乳腺癌细胞生长情况及对癌组织中Th1和Th2平衡的改变，分析通过调节Th1/Th2平衡达到抗肿瘤作用的机制。  方法  将含CD40ScFv基因片段的重组质粒转化至Rosetta大肠杆菌中，诱导表达并经纯化后获得有功能的CD40ScFv蛋白，行SDS-PAGE和Western blot检测。体外培养小鼠乳腺癌4T1细胞，在Balb/C小鼠皮下成瘤建立模型，分为CD40ScFv组、CD40mAb组和生理盐水组（NS组），分别给予CD40ScFv、CD40mAb和生理盐水，观察各组小鼠肿瘤体积的变化。取出瘤体组织，ELISA法检测肿瘤组织上清中IL-12的浓度。提取肿瘤组织浸润淋巴细胞（TILs），应用流式细胞技术检测TILs中Th1与Th2的比例。  结果  诱导表达的CD40ScFv鉴定表达成功，分子大小约为27 KDa，蛋白纯化后经BCA测定浓度为1.12 mg/mL。CD40ScFv组与CD40mAb组肿瘤大小分别为（3.044±0.239）cm3与（2.749±0.261）cm 3，均小于NS组的（3.933±0.326）cm3，差异具有统计学意义（P <0.05）。CD40ScFv组、CD40mAb组肿瘤组织中IL-12浓度分别为（396.27±48.13）pg/mL、（457.63±58.37）pg/mL，均显著高于NS组的（79.51±14.97）pg/mL，差异具有统计学意义（P <0.05）。CD40ScFv组与CD40mAb组的Th1/Th2细胞比值分别为6.32±0.87与5.54±0.71，均显著高于NS组的1.79±0.38，差异具有统计学意义（P < 0.05）。  结论  激动性CD40抗体在体内通过调节Th1与Th2的比例，发挥抑制肿瘤生长的作用，其中通过促进DC活化后分泌IL-12是影响肿瘤微环境中Th1/Th2平衡的重要机制之一。      

调节性T细胞及Th1/Th2细胞因子在急性白血病中的表达及意义

目的:探讨调节性T细胞（Tregs）及Th1/Th2型细胞因子在急性白血病发病中的作用。方法:采用流式细胞术检测37例急性白血病患者［包括急性髓细胞性白血病（acute myeloid leukemia,AML）24例,急性淋巴细胞白血病（acute lymphocytic leukemia,ALL）13例］及28例健康对照者外周血CD4+CD25+Foxp3+Tregs的比例,酶联免疫吸附法（ELISA）法检测血浆IL-2、IFN-γ、IL-10、IL-4和TGF-β水平。结果:AML和ALL患者外周血CD4+CD25+Foxp3+Tregs比例均高于健康对照组 (P＜0.05);AML及ALL患者血浆IL-4、IL-10和TGF-β水平均较健康对照组升高 (P＜0.05);IFN-γ水平较健康对照组降低 (P＜0.05);IL-2水平与健康对照组比较无明显差异 (P＞0.05)。结论:Tregs与Th1/Th2细胞因子同时参与了急性白血病的发生;急性白血病患者机体Th1/Th2细胞因子失衡,Th2占优势状态,这可能是导致急性白血病细胞免疫逃逸的原因之一;Tregs可能通过影响Th1/Th2细胞因子平衡参与急性白血病的发病。     

骨转移癌患者Th1/Th2亚群研究

目的：观察骨转移癌患者Ｔ淋巴细胞亚群中Ｔｈ１／Ｔｈ２的变化,为细胞因子免疫治疗提供依据。方法：应用放射免疫分析及酶联免疫分析检测３０例骨转移癌患者血清中ＩＬ－２、ＩＬ－４、ＩＬ－６、ＩＬ－１０、ＩＬ－１２的含量,检测外周血单个核细胞有或无植物血凝素（ＰＨＡ）存在情况下培养上清中ＩＬ－２、ＩＬ－４含量。结果：骨转移癌患者血清及培养上清中ＩＬ－２、ＩＬ－１２减少（Ｐ＜０．００１）,而ＩＬ－１０、ＩＬ－     

初诊多发性骨髓瘤患者T细胞亚群和骨髓瘤细胞中PD-1、PD-L1及PD-L2的表达与意义

目的 探讨程序性死亡受体-1(PD-1)、程序性死亡配体-1/2(PD-L1/2)在初诊多发性骨髓瘤(NDMM)患者骨髓T细胞亚群和骨髓瘤细胞中的表达水平及其与临床特征的关系.方法 收集22例NDMM患者及18例健康对照组骨髓及临床资料,利用流式细胞术分选CD4+、CD8+T细胞及骨髓瘤细胞,观察PD-1、PD-L1/...     

淋巴瘤与实体瘤患者Th1/Th2漂移状况比较

目的 比较淋巴瘤患者与实体瘤患者Th1/Th2的漂移状况,建立淋巴瘤生物治疗过程中免疫功能有效检测指标.方法 采集患者全血,淋巴瘤10例,实体瘤172例(其中上消化道恶性肿瘤36例;结直肠癌64例;肺癌43例,其他恶性肿瘤29例,健康对照30例.检测首先用刺激剂刺激细胞,增加细胞内因子表达,用荧光标记的特异性抗细胞因子单克隆抗体,特异性抗原抗体结合,最后应用流式细胞仪分析特异性细胞因子表达水平.结果 淋巴瘤与健康人外周血CD+4T细胞表达IFN-γ、IL-4阳性百分比以及IFN-γ/IL-4比值,差异均具统计学意义(P<0.05).淋巴瘤患者Th1/Th2(CD:胞内细胞因子INF-α/IL4)比值较上消化道肿瘤(食管和胃)明显降低差异具统计学意义(P=0.023);淋巴瘤与其他实体瘤(结直肠癌、肺癌、肾癌、乳腺癌及其他肿瘤)差异无统计学意义,但有下降趋势.结论 淋巴瘤患者免疫功能较实体瘤患者有降低趋势,免疫治疗是辅助化疗的必要途径,Th1/Th2(INF-α/IL4)比值有望成为有效的检测指标.

Abstract：

Objective To compare Th1/Th2 drift situation in patients with lymphoma with that in patients with solid tumors, and establish the effective immune function detectable criterion of lymphoma in biological treatment process. Methods The whole blood samples of 10 patients with lymphoma, 202 patients with solid tumors including 36 patients with upper digestive tract cancer, 64 colorectal cancer, 43 lung cancer and 20 the other malignancies, and 30 healthy persons as controls were collected. Stimulation agent was used to stimulate the cells in order to increase cell factor expression and fluorescent labeled specific anti-cytokine monoclonal antibody was used to bind with specific antigen. The expression of specific cytokines was detected by flow cytometry. Results Positive percentages of IFN- γ and IL-4 and ratio of IFN- γ /IL-4 in CD+4 T cells of human peripheral blood had statistically differences between in patients with lymphoma and controls (P < 0.05). The ratio of Thl/Th2 (CD+4 intracellular cytokine INF-α/IL-4) in patients with lymphoma was lower than that in patients with upper digestive tract cancers (esophagus and stomach cancers) (P = 0.023), however, had no statistical differences with that in patients with other solid tumors (colorectal, lung, kidney, breast and other tumors), but had a downward trend. Conclusion Immune functions in patients with lymphoma are lower than those in patients with solid tumors and immune treatment is a necessary to adjuvant chemotherapy. The ratio of Th1/Th2 (INF- α/IL-4) is expected to become effective detection criterion.     

The effect of 1,2-dimethylhydrazine (DMH) carcinogenesis on peripheral T cell subsets in the Wistar Furth rat

1,2-dimethylhydrazine (DMH)-induced colon cancer in Wistar/Furth (W/Fu) rats is analogous in many ways to human colorectal cancer. As part of our attempt to understand the immunobiology of these tumors, we have utilized the recently available monoclonal antibodies W3/25 and OX8 to monitor helper (Th) and suppressor (Ts) lymphocyte subpopulations. Normal untreated male W/Fu rats of less than 1 year of age were phenotyped (n = 43). The mean percentage of Th and Ts was 42 +/- 1 (mean +/- SEM) and 33 +/- 1, respectively. The mean Th/Ts ratio was 1.3 +/- 0.1. A Th/Ts equal to or greater than 1 is considered "normal" in the W/Fu rat. The DMH-treated rats (20 mg/kg/wk) were evaluated in initial experiments at various intervals after treatment. Rats studied 24 hours after a single DMH injection had no alterations in T cell subsets. Rats studied 28, 32, and 65 weeks after the start of 16 weekly DMH injections were found to have a decrease in the percentage of Th and a relative increase in Ts, with Th/Ts ratios of 0.6 +/- 0.2, 0.7 +/- 0.1, and 0.7 +/- 0.1, respectively (each P less than 0.01). In a separate experiment in which rats were studied after 4, 8, and 16 weeks of DMH injections, no alterations in T cell subsets were noted. Rats (n = 5) studied at 20 weeks after the start of DMH were found to have 41 +/- 3% Th and 36 +/- 2% Ts and a Th/Ts ratio of 1.2 +/- 0.1. Three of five rats were found to have adenocarcinomas. Four of five rats had Th/Ts less than 1. One rat with Th/Ts equal to 0.9 had metastatic disease. Rats studied at 25 weeks (n = 8) were found to have more advanced carcinomas (4/8) that were causing obstruction or bleeding in the animal. There was a significant decrease in Th and Ts in this group, with 24 +/- 3% and 26 +/- 3% respectively (P less than 0.001). The Th/Ts ratio for this group was 0.9 +/- 0.1 (P less than 0.01). In other experiments, rats were treated with DMH or placebo over a 16-week period and serially bled during and after treatment. No effect of DMH treatment on T cell subsets was noted. Repeated bleeding alone was noted to cause persistent alterations of T cell subpopulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

宫颈癌患者Th1／Th2细胞因子表达水平的研究

  目的 检测宫颈癌患者外周血CD+4 T细胞分泌细胞因子的水平变化，分析Th1和Th2细胞的细胞因子免疫活动，为肿瘤的免疫治疗提供实验依据。方法 用刺激物刺激细胞，增加细胞内细胞因子的表达，再加入荧光标记的特异性抗细胞因子单克隆抗体，特异性抗原抗体结合，以流式细胞仪分析特异性细胞因子表达水平。结果 宫颈癌患者Th1型细胞因子白细胞介素-2（IL-2）表达水平较正常对照组降低，差异有统计学意义，而Th1 型细胞因子干扰素-γ（IFN-γ）表达水平较正常对照组差异无统计学意义。Th2型细胞因子白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）表达水平较正常对照组显著升高，差异有显著性意义。结论 宫颈癌患者Th1型反应模式处于弱势状态，Th2型反应模式处于优势状态，Th1／Th2平衡失调，Th1／Th2平衡向Th2方向漂移，这可能是肿瘤细胞发生免疫逃逸，从而导致肿瘤的发生或者转移的原因之一。