旋毛虫对不同肠炎模型小鼠脾脏淋巴细胞Th1/Th2水平的影响

目的：研究旋毛虫（T.spiralis）对肠炎小鼠［三硝基苯磺酸（TNBS）或唑酮（OXZ）诱导］脾脏淋巴细胞中Th1/Th2水平的影响。方法：雌性BALB/c小鼠,随机分为50%乙醇对照组、TNBS(OXZ)诱导肠炎模型组、预先感染T.spiralis后诱导TNBS(OXZ)模型组,每组小鼠取材时保证6只以上。对各组小鼠脾脏淋巴细胞进行分离,采用流式细胞术观察TNBS（OXZ）诱导肠炎模型组和预先感染T.spiralis后诱导TNBS（OXZ）模型组。造模后3 d和7 d脾脏淋巴细胞中Th1/Th2水平的变化。结果：与模型组相比,预先感染T.spiralis后诱导TNBS肠炎第3天脾脏Th1/Th2比值未见明显下降（P>0.05）,于第7天明显降低（P<0.05）。诱导OXZ肠炎模型后第3天及第7天小鼠脾脏Th1/Th2比值均明显低于T.spiralis干预组（P<0.05）。结论：针对TNBS 肠炎模型,T.spiralis可能是通过诱导Th2及Tr1型免疫反应抑制模型小鼠过度的Th1型免疫而起到良好的干预作用。在T.spiralis对OXZ模型小鼠的干预性研究中,并无T.spiralis感染诱发的Th2型炎症反应加重同样以Th2升高为主的OXZ模型小鼠的病情。     

旋毛虫对三硝基苯磺酸诱导的实验性小鼠肠炎模型的干预研究

目的 研究旋毛虫对三硝基苯磺酸（TNBS）诱导的实验性小鼠肠炎模型的影响及其免疫作用机制。方法观察感染和未感染旋毛虫小鼠于TNBS诱导肠炎后3d及7d不同指标的变化，包括小鼠生存率、疾病活动指数（DAI）、结肠大体损伤和病理损伤评分、炎症指标髓过氧化物酶（MPO）活性检测，结肠细胞因子IFN-γ和IL-4 mRNA的表达量分析。结果 预先感染旋毛虫后诱导TNBS模型组小鼠在造模后3d及7d与单纯模型组相比小鼠生存率升高（P〈0．05），DAI、结肠大体损伤和病理损伤评分及MPO活性下降（P〈0．05），结肠中IFN-γmRNA的表达量下调（P〈0．05），而IL-4 mRNA的表达量增加（P〈0．05）。结论 旋毛虫对TNBS诱导的实验性小鼠肠炎具有良好的干预作用，其免疫作用机制可能是通过下调炎症性肠病过度的．TH1型免疫反应、上调TH2型免疫反应而实现的。     

黄芩茎叶总黄酮对胶原性关节炎小鼠Th1/Th2细胞平衡的调节

目的观察黄芩茎叶总黄酮对Ⅱ型胶原诱导性关节炎小鼠脾淋巴细胞Th1、Th2及其相关细胞因子IL-10、IFN-γ的影响,初步探讨黄芩茎叶总黄酮对类风湿性关节炎的作用。方法选用C57BL/6小鼠,建立鸡Ⅱ型胶原诱导性关节炎小鼠模型,将造模成功的小鼠随机分为CIA模型组、黄芩茎叶总黄酮组、雷公藤多苷组,另设正常对照组,于初次免疫后第21天开始灌胃给药,35 d后流式细胞术检测小鼠脾淋巴细胞Th1、Th2水平及相关细胞因子IL-10、IFN-γ的表达。结果与模型组比较,药物组小鼠CD4+T淋巴细胞中Th1细胞数量明显降低(P0.05),Th2比例增加(P0.01),药物组IL-10分泌显著增多(P0.05),IFN-γ分泌明显减少(P0.05),2用药组无明显差异(P0.05)。结论黄芩茎叶总黄酮可以调节Th1/Th2的平衡及其相关细胞因子IFN-γ、IL-10的表达。     

多形螺旋线虫对T细胞诱导的小鼠肠炎CD4+T细胞分泌和浸润的影响

目的 研究多形螺旋线虫对T细胞诱导的小鼠肠炎CD4+T细胞分泌和浸润情况的影响.方法 用卵清蛋白(OVA)特异性的CD4+辅助性T细胞(Th)转入SCID小鼠中制作小鼠实验性肠炎模型.将实验模型小鼠分为多形螺旋线虫感染组和无感染组,观察感染14 d小鼠结肠炎性反应的组织学病理变化;应用实时荧光定量PCR检测感染14 d 小鼠结肠组织中γ干扰素(IFN-γ)、白细胞介素4(IL-4)、肿瘤坏死因子α(TNF-α)的表达;以免疫荧光法观察感染3、5、7、14d小鼠结肠组织中CD4+T细胞的数量.结果 与无感染组比较,感染组小鼠结肠炎性反应明显加重,病理评分升高(5.41±0.53比2.12±0.69,P＜0.05).感染组小鼠IL-4、TNF-α较无感染组明显增高,IFN-γ则明显减低(IL-4:10.70±4.85比1.00±1.07,TNF-α:6.54+2.88比1.00±0.48,IFN-γ:0.21±0.10比1.00±0.28,均P＜0.05).各时间点感染组SCID小鼠结肠组织中CD4+T细胞均比同时间点的无感染组明显增多,CD4+T细胞浸润明显增强.结论 多形螺旋线虫感染在CD4+T细胞诱导的小鼠实验性肠炎的早期阶段促进了炎性反应的加重,可能与促进CD4+T细胞浸润、诱导Th2和抑制Th1的分泌有关.     

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.     

小鼠皮下感染着色芽生菌病皮损中局部细胞免疫功能研究

目的 利用小鼠皮下着色芽生菌病模型,研究在不同的病程发展阶段其T细胞免疫功能的变化.方法 足垫局部皮下注射法建立小鼠的裴氏着色霉感染的着色芽生菌病模型,通过免疫组织化学技术,检测正常小鼠足垫皮肤皮损局部细胞因子IFN-γ、IL-4、IL-10、TNF-α的表达并作为对照组,观察免疫正常组和环磷酰胺免疫抑制处理的免疫抑制组小鼠分别在感染上述真菌后7 d、30 d时,皮损局部细胞因子水平变化,并与对照组比较.结果 在着色芽生菌病小鼠模型中,第7天时,免疫正常组IL-4、TNF-α和IL-10较正常对照组均出现了显著的升高(P＜0.01),表现为Th1和Th2型细胞免疫均增强的模式,并以Th2型为主;30 d时IL-10表达显著下降(P＜0.01),与同期正常对照组比较差异无统计学意义(P=0.52),IFN-γ、TNF-α水平比7 d时显著升高(P＜0.01),表现为Th2型细胞免疫减弱Th1型占主导的模式.免疫功能受损组第7天时IL-10、IL-4的水平升高与其他两组相比差异均有统计学意义(P＜0.01),IFN-γ表达水平则明显下降(P＜0.01),TNF-α的表达与正常对照组相比差异无统计学意义(P=0.39),表现为Th2型细胞免疫增强Th1功能受抑模式;30 d时,IL-10表达水平较7 d时显著减少,但仍然高于同期的免疫正常组和正常对照组,IFN-γ、TNF-α水平显著升高(P＜0.01),但却低于免疫正常组,表现为Th2型免疫模式渐弱Th1功能逐渐增强模式.结论 在不同免疫状态下小鼠着色芽生菌病感染的过程中,随着病情好转存在由Th2型细胞免疫为主导转化为Th1型细胞免疫功能占主导的过程,免疫抑制下主要表现为Th1反应受抑制,Th1型细胞因子在控制着色芽生菌病的发展过程中具有关键性的保护作用,Th2型细胞因子则可能与感染的发展进程相关.     

IL-12对BALB/c小鼠Th17细胞的分化的影响

目的: 观察细胞因子IL-12对Th17细胞分化的影响.方法: 小鼠脾淋巴细胞经抗CD3单克隆抗体(mAb)和不同浓度的重组小鼠IL-12刺激, 3 d后使用ELISA方法观察培养物上清液中IL-17的产生情况.并使用细胞内细胞因子染色的方法, 通过流式细胞术观察CD3 mAb和重组小鼠IL-12刺激对Th1和Th17细胞分化的影响.结果: Th17细胞不分泌IFN-γ、 IL-5、 IL-10等细胞因子, 不表达Foxp3, 是一个独立的细胞亚群.不同浓度的重组小鼠IL-12可以诱导抗CD3 mAb 的T细胞分泌IFN-γ, 并向Th1细胞方向分化.同时, IL-12可以抑制活化的T细胞分泌IL-17, 抑制T细胞向Th17细胞分化.结论: IL-12可以抑制Th17细胞的分化.     

李斯特菌上调约氏疟原虫感染鼠疟模型的Th1应答效应

目的探讨李斯特菌(Listeria monocytogenes,Lm)对致死型约氏疟原虫(Plasmodium yoelii 17XL,P.y 17XL)感染小鼠的免疫应答调节机制。方法小鼠腹腔注射感染疟原虫2 d后尾静脉分别接种Lm及热灭活李斯特菌(heat-killed Lm,HKLm),对照组单独感染疟原虫,统计小鼠虫血症及生存率。感染后处死小鼠,流式细胞术检测脾细胞内细胞因子IFN-γ,Real-time PCR检测细胞因子IL-4、IL-10、IL-12p40、IFN-γ分泌水平,Griess反应检测脾细胞上清中一氧化氮(NO)含量。结果与对照组相比,Lm接种组的虫血症水平明显降低,P.y 17XL感染后5 d,CD4+、CD8+T细胞分泌的IFN-γ水平明显升高,巨噬细胞活化,NO产生增加。P.y17XL感染后3 d(Lm接种后1 d),Lm接种组比HKLm接种组IFN-γ水平升高显著,HKLm接种组虫血症水平与对照组基本一致。结论本研究表明Lm通过增强P.y 17XL感染小鼠的Th1应答对疟疾感染起到一定的免疫保护作用,并且这种保护作用与感染早期诱导IFN-γ分泌有关。这对于进一步以Lm为疫苗载体或佐剂研制抗疟新药具有重要的科学指导意义。     

美沙拉嗪对DSS诱导小鼠溃疡性结肠炎模型Th1、Th17及Treg细胞亚群的影响

 目的:观察葡聚糖硫酸钠（DSS）诱导小鼠溃疡性结肠炎（UC）模型中辅助性T细胞（Th1、Th17亚群）及调节性T细胞（Treg）细胞亚群的变化,探讨美沙拉嗪（MSLZ）治疗UC的免疫学机制。方法: 采用流式细胞分析术检测DSS诱导的小鼠UC模型结肠组织及外周血单个核细胞中白细胞介素17（IL-17）、γ-干扰素（IFN-γ）及核转录因子Foxp3的表达,并检测MSLZ预治疗对小鼠UC 模型Th1、Th17和Treg亚群的影响。结果: 在DSS诱导的小鼠UC模型中,其外周血单个核细胞（PBMC）中CD3+T细胞高表达IL-17、IFN-γ及Foxp3,肠黏膜单个核细胞（LPMC）中CD3+T细胞高表达IFN-γ和Foxp3,但IL-17的表达与对照组无差异。进一步发现UC模型小鼠LPMC中Th17、Th1和Treg均显著高于对照组,但PBMC中只有Treg高于对照组。MSLZ预治疗能显著下调UC 模型小鼠PBMC和LPMC中Th17、Th1和Treg细胞亚群。结论: DSS诱导的小鼠 UC模型中CD4+T细胞亚群Th1、Th17及Treg细胞显著升高,提示CD4+T细胞亚群在UC发病中起重要作用,美沙拉嗪可能通过调节Th1、Th17及Treg细胞亚群发挥抗炎及治疗UC作用。     

束缚应激对S180荷瘤小鼠Th1/Th2型细胞因子及肿瘤生长的影响

目的:观察束缚应激对荷S180瘤小鼠Th1/Th2型细胞因子及肿瘤生长的影响。方法:取腹腔传代第7天的肿瘤细胞S180,调细 胞密度至1×1010/L,注射于昆明小鼠右腋皮下,每只0.2 mL。接种后束缚限制活动,8 h/d,并设单纯束缚组、单纯肿瘤组和正常对照组。10 d后处死小鼠,剥取肿瘤称瘤重,计算胸腺指数,分别采用MTT比色法和丝裂原激活淋巴母细胞法检测脾T细胞增殖及产生Th1型细胞因子IL-2、IFN-γ的能力,并取血清用ELISA法检测Th2型细胞因子IL-4、IL-10的含量。结果:束缚应激可明显增加荷瘤小鼠的瘤重(P<0.01),降低小鼠胸腺指数和脾T细胞的增殖能力(P值分别<0.01),降低荷瘤小鼠脾细胞产生IL-2和IFN-γ的能力(P值分别<0.01),并可使小鼠血清IL-4、IL-10的含量明显增加(P值分别<0.01和<0.05)。结论:束缚应激可显著抑制荷瘤小鼠的细胞免疫功能,使产生Th1型细胞因子的功能减弱,Th2型细胞因子的含量增加,导致Th1/Th2细胞的平衡进一步向Th2细胞漂移。这可能是其促进肿瘤生长的重要机制。     

Host protective immunity to Trichinella spiralis in mice: activation of Th cell subsets and lymphokine secretion in mice expressing different response phenotypes.

Host protective immunity to the intestinal dwelling nematode Trichinella spiralis is mediated by CD4+ mesenteric lymph node (MLN) cells during the course of intestinal infection. The present study has examined the cytokine production by T cells within the MLN of two H-2-compatible strains of mice infected with T. spiralis which differ in the speed at which they expel the parasite from the gut. For both strains of mice, in vitro stimulation of MLN cells with a protective worm antigen preparation resulted in secretion of elevated levels of interleukin-3 (IL-3), IL-4, IL-5 and IL-9 compared to controls. Negligible levels of interferon-gamma (IFN-gamma) were secreted. Furthermore, a similar pattern of cytokine secretion was observed from MLN cells taken from infected mice after in vitro stimulation by T-cell mitogens. No evidence was found for a relationship between quantity of cytokine secreted and the differences in speed of parasite expulsion in the two strains of mice studied. The results support the hypothesis that protective immunity to T. spiralis infection is associated with the activation of Th2-type cells within the MLN in the relative absence of Th1-type cells.     

The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection

Trichinella spiralis and Trichuris muris are nematode parasites of the mouse, dwelling in the small and large intestines, respectively: worm expulsion requires development of a Th2 immune response. The chemokine CCL11 is agonist for the chemokine receptor CCR3 and acts in synergy with IL-5 to recruit eosinophils to inflammatory sites. The role of CCL11 in gastrointestinal helminth infection has not been previously studied. We challenged wild-type (WT) BALB/c, CCL11 single knockout (SKO) and CCL11 IL-5 double knockout (DKO) mice with either T. spiralis muscle larvae or T. muris eggs in order to examine eosinophil recruitment to the small and large intestine during helminth infection. A peripheral eosinophilia was seen in WT and SKO mice during T. spiralis infection but not with T. muris. Gastrointestinal eosinophilia was markedly reduced but not ablated in SKO mice -- and negligible in DKO mice -- infected with either nematode. The residual eosinophilia and up-regulation of CCL24 mRNA in the gastrointestinal tract of SKO mice infected with either nematode, together with the presence of an eosinophil-active factor in T. spiralis and T. muris products, suggest that CCL11 is the salient but not the sole eosinophil chemoattractant of biological significance during gastrointestinal helminth infection.     

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。     

Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines

Oral administration of DSS has been reported to induce an acute and chronic colitis in mice. The aim of our study was to evaluate if the chronic phase of DSS-induced colitis was characterized by a Th1/Th2 response and how this would relate to mucosal regeneration. Swiss Webster mice were fed 5% DSS in their drinking water for 7 days, followed by 2–5 weeks consumption of water. Control mice received only water. The animals were killed at 3 and 6 weeks after induction. Their colons were isolated for histology and immunohistochemistry, using specific MoAbs for T and B cells, macrophages, interferon-gamma (IFN-γ), IL-4 and IL-5. Colons were scored for inflammation, damage and regeneration. Two weeks after stopping DSS the colonic epithelium had only partially healed. Total colitis scores were still increased, especially in the distal colon, which was due to more inflammation, damage and less regeneration. In areas of incomplete colonic healing the basal parts of the lamina propria contained macrophages and CD4⁺ T cells. These CD4⁺ T cells showed a focal increase of IFN-γ and IL-4 staining compared with control animals. These findings were still observed 5 weeks after stopping DSS in some mice, albeit less extensive. Chronic DSS-induced colitis is characterized by focal epithelial regeneration and a Th1 as well as Th2 cytokine profile. We postulate that chronic immune activation mediated by both populations of Th cells can interfere with colonic healing and can play a role in the pathogenesis of chronic colitis.     

Toxoplasma gondii infection inhibits Th17-mediated spontaneous development of arthritis in interleukin-1 receptor antagonist-deficient mice

Interleukin 1 receptor antagonist (IL-1Ra)-deficient BALB/c mice develop spontaneous arthritis resembling human rheumatoid arthritis. We herein report that infection with Toxoplasma gondii, an intracellular protozoan, is capable of ameliorating the spontaneous development of arthritis in IL-1Ra-deficient mice. The onset of arthritis development was delayed and the severity score of arthritis was significantly suppressed in T. gondii-infected mice. Expression of IL-12p40 mRNA from CD11c(+) cells of mesenteric lymph nodes (mLN) and spleen markedly increased at 1 week after peroral infection. While CD11c(+) cells also produced IL-10, IL-1β, and IL-6, CD4(+) T cells from T. gondii-infected mice expressed significantly high levels of T-bet and gamma interferon (IFN-γ) mRNA in both mLN and spleen. Levels of GATA-3/IL-4 mRNA or RORγt/IL-17 mRNA decreased in the infected mice, indicating Th1 cell polarization and the reduction of Th2 and Th17 cell polarization. The severity of arthritis was related to Th1 cell polarization accompanied by Th17 cell reduction, demonstrating the protective role of the T. gondii-derived Th1 response against Th17 cell-mediated arthritis in IL-1Ra-deficient mice.     

Mast cells promote Th1 and Th17 responses by modulating dendritic cell maturation and function

Mast cells (MCs) play an important role in the regulation of protective adaptive immune responses against pathogens. However, it is still unclear whether MCs promote such host defense responses via direct effects on T cells or rather by modifying the functions of antigen-presenting cells. To identify the underlying mechanisms of the immunoregulatory capacity of MCs, we investigated the impact of MCs on dendritic cell (DC) maturation and function. We found that murine peritoneal MCs underwent direct crosstalk with immature DCs that induced DC maturation as evidenced by enhanced expression of costimulatory molecules. Furthermore, the MC/DC interaction resulted in the release of the T-cell modulating cytokines IFN-γ, IL-2, IL-6 and TGF-β into coculture supernatants and increased the IL-12p70, IFN-γ, IL-6 and TGF-β secretion of LPS-matured DCs. Such MC-"primed" DCs subsequently induced efficient CD4+ T-cell proliferation. Surprisingly, we observed that MC-primed DCs stimulated CD4+ T cells to release high levels of IFN-γ and IL-17, demonstrating that MCs promote Th1 and Th17 responses. Confirming our in vitro findings, we found that the enhanced disease progression of MC-deficient mice in Leishmania major infection is correlated with impaired induction of both Th1 and Th17 cells.     

The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis

Inflammatory bowel diseases are characterized by disabilities in gastrointestinal system and defects in mucosal immune system. Statins are 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor and are used to treat hypercholesterolemia in patients with coronary artery and atherosclerotic diseases. Recent studies have demonstrated that statins have immunomodulatory role by effecting different pathways in immune system. In this study, we investigated the effect of atorvastatin and its mechanism on systemic immune response in treatment of trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We observed that atorvastatin significantly suppressed the severity of TNBS-induced colitis in BALB/c mice. This was manifested in reduced rectal bleeding, decrease in colon length, reduction of histological damage, and improved survival. Concurrently, we investigated the immunomodulatory role of atorvastatin on systemic immune system. We investigated the proinflammatory (IL-1α, IL-6, TNF-α), Th1 (IFN-γ, IL-2), Th2 (IL-4, IL-5, IL-10), and Th17 (IL-17, IL-23) cytokine levels in serum samples of colitis and atorvastatin-administered mice. We discovered that administration of atorvastatin significantly down-regulates systemic TNF-α level and Th17 cytokine levels. Furthermore, atorvastatin treatment switches Th1 type T-cell response toward/to Th2 (IL-4, IL-10) type response.     

Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of inflammatory bowel disease

4-1BB (CDw 137), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor primarily expressed on activated T cells. It has been shown that the administration of agonistic anti-4-1BB monoclonal antibody (mAb) enhances tumor immunity and allogenic immune responses. Paradoxically, we found that the administration of anti-4-1BB mAb reduced the incidence and severity of inflammatory bowel disease. In this study, we investigated the effects of anti-4-1BB mAb in a murine intestinal inflammation model, which induced by the hapten reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS) and mimics immunologic characteristics of human Crohn's disease (CD). Colitis was induced by rectal administration of 2mg of TNBS in 35% ethanol using a vinyl catheter positioned 4cm from the anus. All mice were sacrificed 3 and 10 days after the TNBS administration. The disease activity index (DAI), histological changes of the colon and production of cytokines (IL-2, IL-4, IL-10 and IFN-gamma) were evaluated. The surface molecules of T cells in peripheral blood, spleen and mesenteric lymph nodes were analyzed by flow cytometry. When mice were treated with anti-4-1BB mAb, improvement in both wasting and histopathologic signs of colonic inflammation was observed. The increase a number of splenic CD4(+)CD25(+) T cells and decreased synthesis of the Th1 cytokine IL-2 also occurred. Interestingly, increased production of Th1 cytokine IFN-gamma and proportion of CD8(+) T cells were observed in mice treated with anti-4-1BB mAb in comparison to the colitic mice. These studies show, for the first time, that agonistic anti-4-1BB mAb can improve experimental colitis by reduction of IL-2 and augmentation of CD4(+)CD25(+) regulatory T cells. TNBS colitis is Th1-mediated and has similar histologic features and distribution of inflammation to CD. This study suggests that anti-4-1BB mAb therapy could be effective in the treatment of patients with CD.