玉屏风散对S180荷瘤小鼠肿瘤生长及免疫功能的影响

目的:探讨玉屏风散对荷瘤小鼠肿瘤生长及免疫功能的影响.方法:采用体外培养S180肉瘤细胞,接种健康小鼠,建立荷瘤小鼠模型,并给予玉屏风散治疗,观察计算抑瘤率,检测巨噬细胞吞噬活性,巨噬细胞NO分泌量,自然杀伤细胞(NK)活性,T淋巴细胞增殖能力及白介素-2(IL-2)的产生及活性.结果:玉屏风散可提高荷瘤小鼠吞噬细胞的功能,增加巨噬细胞NO分泌量,促进荷瘤小鼠白介素-2(IL-2)的产生,淋巴细胞的转化、及NK细胞活性.结论:玉屏风散可增强荷瘤小鼠的免疫功能,抑制模型鼠肿瘤的生长.     

甲状腺激素对小鼠脾淋巴细胞增殖反应和IL-2生成的影响

给小鼠用丙基硫氧嘧啶(PTU)抑制其体内甲状腺激素的合成以制备实验性“甲低”小鼠模型。该鼠脾淋巴细胞的增殖反应及白细胞介素II(IL-2)的生成均明显低于对照小鼠,给“甲低”小鼠补充不同剂量的L-T_4后,其脾淋巴细胞增殖反应随血中T_3、T_4水平的恢复呈剂量依赖性增强,当剂量过大(10mg/kg)时,血中T_3、T_4含量明显高于正常,此时,脾淋巴细胞增殖反应反而下降。将正常小鼠的脾淋巴细胞在体外培养,加入L-T_2(10~(14)～10~(-6)或L-T_4(10~(-12)～10~(-4)均可剂量依赖性地促进ConA诱导的脾淋巴细胞增殖,分别在10~(-10)M及10~(-2)M时达最大效应,剂量进一步增加,增殖反应反而下降,这与体内实验结果基本一致。在加了L-T_4且经48小时培养的脾淋巴细胞上清液中未检出T_3,表明L-_4不需转变为T_3即可发挥作用,即T_3、T_4均能直接影响脾淋巴细胞的增殖。本实验结果证明甲状腺激素在体内外均能促进T淋巴细胞增殖,其机制与促进IL-2生成有关。     

玉屏风散对S180荷瘤小鼠Th1／Th2型细胞因子的影响

目的探讨玉屏风散对荷瘤小鼠Th1／Th2型细胞因子产生的影响。方法采用体外培养S180肉瘤细胞，接种C57BL／6纯系小鼠，建立荷瘤小鼠模型，设正常对照、荷瘤对照及玉屏风散给药组，检测各组脾脏T淋巴细胞增殖能力及Th1（IL-2、IFN-γ）和Th2（IL-4、IL-10）细胞因子产生水平。结果荷瘤组T细胞增殖能力明显下降，Th2型细胞因子IL-10的产生明显增加，与正常对照组比较均有统计学意义（P〈0．01），而IL-4的含量略有增加，但无统计学意义。Th1型细胞因子IL-2及IFN-γ的产生明显减少，与正常对照组比较有统计学意义（P〈0．01，P〈0．05）。玉屏风散给药对T细胞增殖能力及细胞因子的产生有较为明显的调节作用，与荷瘤组比较T细胞增殖能力及IL-2、IFN-γ的产生明显增加（P〈0．01），Th2型细胞因子IL-10的血清含量下降（P〈0．01）．IL-4的含量略有下降，但与荷瘤对照组比较无统计学意义。结论玉屏风散可有效调节荷瘤小鼠的免疫功能，促进荷瘤鼠Th1型细胞因子的产生，有效纠正荷瘤导致Th1／Th2的失衡，增强机体的抗肿瘤免疫功能。     

IL-2对荷瘤小鼠红细胞免疫粘附功能及抑瘤生长的研究

ＩＬ-２对荷瘤小鼠红细胞免疫粘附功能及抑瘤生长的研究曹卉，明建扩，吕厚东（济宁医学院微生物学教研究室济宁２７２１１３）柳青，曹蕊（济宁肿瘤医院放疗科济宁２７２１０３）近几年的研究表明，白细胞介素２（ＩＬ-２）对红细胞免疫功能也有提高作用［１￣３］。本文...     

热化疗对荷瘤小鼠淋巴细胞转化指数及IL—2活性的影响

热化疗作为一种肿瘤治疗的新方法 ,其有效性已得到公认 [1 ] ,人们普遍认为它的作用是广泛的。热化疗除了直接杀伤肿瘤细胞以及增强局部化疗药效外 [2 ] ,还可以刺激免疫系统的功能 ,增加 CD3+ T、CD4+ T细胞的数量 ,提高 CD4+ /CD8+ 的比值 [3 ,4] ,但是其对 T细胞功能状态有无改善尚不清楚。本实验的目的旨在研究热化疗后 T细胞功能的变化 ,进一步探讨热化疗的机制以及它与单独热疗、化疗相比的优越性 ,以促进其在临床的应用和推广。1　材料与方法1.1　动物　 BAL B/ C纯系小白鼠 5 0只 (华西医科大学钩端螺旋体病研究室提供 ) ,8…     

组胺对T细胞IL-2产生及增殖活性影响的实验研究

目的:了解组胺对 CD4 和 CD8 T细胞IL-2产生和细胞增殖活性的影响。方法:密度梯度离心及吸附法分离PBMC和PBLC,采用抗CD4 和CD8 抗体分别制备CD8 和CD4 T细胞进行培养,然后采用ELISA法和MTT比色法测上清液IL-2含量及增殖活性。结果:①组胺 CD4 （CD8 ）培养上清液中IL-2水平及MTT增殖指数与T细胞自然培养孔比较明显降低（P<0.05）。②组胺 CD4 （CD8 ） 西咪替丁培养孔上清液中IL-2水平及 MTT增殖指数明显高于未加西咪替丁孔（P<0.05）。③CD4 T细胞自然培养孔上清液中IL-2水平显著高于CD8 T细胞自然培养孔。结论:组胺可抑制T细胞IL-2产生及增殖。西咪替丁可阻断组胺对T细胞的抑制作用。CD8 T细胞也可产生IL-2,但其功能较 CD4 T细胞为低。     

GBEE对荷瘤小鼠IL-2、IL-12、TNF-α及TGF-α水平的影响

目的:研究银杏外种皮提取物(GBEE)的抗肿瘤作用及其对荷瘤小鼠免疫功能的影响。方法:采用ICR小鼠,建立S180移植瘤模型,GBEE连续灌胃16天,观察荷瘤小鼠移植瘤抑制率;体外培养荷瘤小鼠脾脏细胞,应用LPS诱生IL-12,应用ConA诱生IL-2;采用双抗体夹心ABC-ELISA法测定IL-12及荷瘤小鼠血清TNF-α含量;采用MTT法检测IL-2活性;采用放射免疫分析法测定荷瘤小鼠血清TGF-α的含量。结果:GBEE可明显抑制小鼠S180移植瘤的生长,其中200 mg/(kg.d)剂量组抑瘤率达38.36%;GBEE可提高荷瘤小鼠血清TNF-α含量,促进脾淋巴细胞IL-12的形成,增强脾脏T淋巴细胞IL-2活性,降低荷瘤小鼠血清TGF-α水平。结论:GBEE可抑制瘤细胞分泌TGF-α,具有显著抗肿瘤作用;可促进细胞因子IL-2、IL-12和TNF-α的生成,具有增强荷瘤机体免疫功能的作用。GBEE的免疫增强效应可能是其发挥抗肿瘤作用的重要途径之一。     

恶性葡萄胎患者化疗前后血清IL-2、SIL-2R和外周血B细胞和T淋巴细胞亚群检测的临床意义

目的:探讨了恶性葡萄胎患者化疗前后血清IL-2、SIL-2R和外周血B细胞及T淋巴细胞亚群水平及临床意义.方法:分别应用放射免疫分析、ELISA法和单克隆抗体法对32例恶性葡萄胎患者进行了血清IL-2、SIL-2R和外周血B细胞及T淋巴细胞亚群进行了检测,并与35名正常健康人作比较.结果:恶性葡萄胎患者在化疗前血清SIL-2R和B细胞数均非常显著地高于正常人(P＜0.01),而IL-2、CD3、CD4、CD4/CD8比值则显著地低于正常人组(P＜0.01),经化疗后6个月,与正常人比较仍有显著性差异(P＜0.05).结论:恶性葡萄胎患者是一种自身调节免疫异常的疾病.     

SBHL对S180荷瘤小鼠肿瘤生长及免疫功能的影响

目的:探讨SBHL对肿瘤的作用效果及其抗肿瘤免疫效应机制。方法:选用S180荷瘤小鼠,采用腹腔注射SBHL[10、30、50mg/(kg·d)],连续注射14天,观察肿瘤生长及SBHL对小鼠免疫功能的影响。结果:SBHL能显著抑制荷瘤小鼠S180肉瘤的生长。SBHL对荷瘤小鼠受抑的细胞免疫功能具有明显正向调节作用,能提高脾淋巴细胞增殖及IL-2产生能力,增强NK和LAK细胞活性。结论:SBHL能明显抑制肿瘤的生长,SBHL的免疫增强效应可能是其发挥抗肿瘤作用的重要途径。     

IL-2 receptor gene expression and IL-2 production by human preterm newborns' cells.

IL-2 receptor (IL-2R) gene expression in human umbilical cord blood mononuclear cells (CBMC) of preterm and term newborns was examined following stimulation for 18 h with phytohaemagglutinin (PHA) and compared with that of adult peripheral blood mononuclear cells (PBMC; mothers and control group). mRNA for IL-2R could not be detected in CBMC of preterm infants, whereas the mRNA levels for IL-2R found in full term neonates were similar to those observed in PBMC of adults. IL-2 activity in conditioned medium (CM) of mononuclear cells stimulated with either optimal or suboptimal PHA concentrations for 24 h and 48 h was also determined. At 24 h of stimulation, IL-2 activity found in CM obtained from CBMC of preterm and term newborns was significantly higher than that found in CM of adults' PBMC. A further enhancement of IL-2 activity (six to eight times) was observed in CM of preterm and term cells stimulated for 48 h, whereas no significant difference was found in IL-2 activity in CM from adult cells tested at the two incubation periods. The present findings may provide an additional explanation for the impaired function of the immune system, and the high susceptibility to infections observed in preterm newborns.     

Tunicamycin inhibits function and expression of the high-affinity IL-2 receptor in a murine IL-2-dependent cell line.

Murine interleukin-2-dependent T-lymphocytes (CT6) were treated with tunicamycin, an inhibitor of both glycoprotein and ganglioside synthesis, to study the involvement of glycosylation in the IL-2 proliferative response. Tunicamycin inhibited proliferation in a dose-dependent manner at concentrations which did not inhibit protein synthesis (10-50 ng/ml). Swainsonine, a glycoprotein processing inhibitor, had no effect on proliferation. Inhibition of proliferation by tunicamycin was accompanied by an inhibition of binding of 125I-IL-2 to its high-affinity receptor. Scatchard analysis showed that receptor number was decreased by tunicamycin treatment. On the other hand, tunicamycin did not affect either the binding of the monoclonal antibody 7D4, specific for the 55 kDa low-affinity protein subunit of the IL-2 receptor, or the recycling of the IL-2 receptor. To determine the specific effects of tunicamycin on the biosynthesis of particular CT6 glycoconjugates, cells were radiolabeled with 3H-glucosamine and incorporation into ganglioside, neutral glycolipid and glycoprotein fractions was measured. Low doses of tunicamycin inhibited ganglioside synthesis and glycoprotein glycosylation to the same extent, whereas no effect on neutral glycolipid synthesis was observed. These results suggest that glycosylation of glycoprotein and/or gangliosides might play an important role in the formation of a functional high-affinity IL-2 receptor complex in CT6 cells.     

IL-10 enhances expression of the IL-2 receptor alpha chain on T cells.

Interleukin-10 (IL-10) has various immunomodulatory actions depending on the target cell type. Some of these effects have been shown to be owing to its ability to down-regulate surface expression of markers, for example HLA-DR on macrophages and CD25 (IL-2 receptor alpha chain) on B cells. In this report we show that preincubation of IL-10 for 24 hr up-regulates expression of the activation marker CD25, but not HLA-DR on cloned T cells of various phenotypes such as CD4+, CD8+, CD4- CD8- alpha beta and gamma delta T-cell receptor (TCR)-expressing cells. This up-regulation of CD25 was accompanied by an increase in the T cells IL-2-dependent proliferative response in 63% of the CD4+ clones and 100% of the CD8+, CD4-, CD8- alpha beta and gamma delta TCR+ clones analysed. IL-10 was also shown to be at least partly responsible for the up-regulation of CD25 on mitogen-activated peripheral blood mononuclear cells, suggesting that IL-10 has this CD25 modulatory effect within a more physiological environment. Our data suggest that IL-10 can have a multitude of effects on human T cells, and should not be considered exclusively as an immunoinhibitory cytokine.     

IL-2基因修饰的肿瘤细胞对小鼠体内巨噬细胞数量和功能的影响

目的探讨IL-2基因修饰的肿瘤细胞对小鼠体内巨噬细胞(Mφ)数量和功能的影响.方法应用腺病毒载体介导的小鼠IL-2基因(Ad-mIL-2)修饰CT26小鼠结肠腺癌细胞(CT26-mIL-2)后皮下接种小鼠,计数小鼠腹腔Mφ的数量,观察其吞噬功能,混合淋巴细胞反应法(MLR)测定其抗原提呈能力,MTT法检测其杀伤活性.结果 mIL-2基因修饰的CT26细胞(CT26-mIL-2细胞)皮下接种后,小鼠腹腔Mφ数量显著增加,吞噬能力明显增强,抗原提呈能力提高,并具有较强的杀伤活性.结论 CT26-mIL-2细胞分泌的IL-2能有效地激活Mφ,这可能是CT26-mIL-2细胞体内致瘤性下降的原因之一.     

IL-2基因修饰的肿瘤细胞对小鼠体内巨噬细胞数量和功能的影响

目的　探讨IL - 2基因修饰的肿瘤细胞对小鼠体内巨噬细胞 (M)数量和功能的影响 .方法　应用腺病毒载体介导的小鼠IL - 2基因 (Ad -mIL - 2 )修饰CT2 6小鼠结肠腺癌细胞 (CT2 6 -mIL - 2 )后皮下接种小鼠 ,计数小鼠腹腔M的数量 ,观察其吞噬功能 ,混合淋巴细胞反应法 (MLR)测定其抗原提呈能力 ,MTT法检测其杀伤活性 .结果　mIL - 2基因修饰的CT2 6细胞 (CT2 6 -mIL - 2细胞 )皮下接种后 ,小鼠腹腔M数量显著增加 ,吞噬能力明显增强 ,抗原提呈能力提高 ,并具有较强的杀伤活性 .结论　CT2 6 -mIL - 2细胞分泌的IL - 2能有效地激活M ,这可能是CT2 6 -mIL - 2细胞体内致瘤性下降的原因之一 .     

Esculetin inhibits T cell activation without suppressing IL-2 production or IL-2 receptor expression

Esculetin (6,7-dihydroxycoumarin) was found to inhibit dose-dependently the proliferation of human T cells stimulated by PHA or phorbolester plus ionomycin. Proliferation in autologous and allogeneic MLR and generation of cytotoxic T cells under limiting dilution conditions were also suppressed, with more than 90% inhibition seen at 50 microM esculetin. The immunosuppressive effect of esculetin was not due to toxicity. Esculetin did not inhibit interleukin-2 (IL-2) production, nor did it interfere with the appearance of IL-2 receptors on stimulated T cells, as judged by immunofluorescence using anti-Tac monoclonal antibody. These results show that esculetin inhibits T-cell activation at a site distal to production of IL-2 and IL-2 receptor expression.