艾氏腹水癌克隆细胞株E2G8建立小鼠动物模型生物学特性研究

目的　比较不同品种 (系 )小鼠接种E2G8细胞株的某些生物学特性。方法　将E2G8细胞稀释成不同浓度 ,接种KM、DBA 2、6 15、C57BL 6及BALB c小鼠皮下或腹腔 ,观察小鼠出现可见肿块 腹水时间及小鼠生存时间 ;测量肿块直径 (cm)及瘤重 ;荷瘤小鼠腹腔注射环磷酰胺 (CTX) ,观察E2G8细胞肿瘤模型对CTX治疗的敏感性。结果　E2G8接种BALB c、6 15小鼠皮下毒性最大 ,DBA 2、C57BL 6小鼠次之 ,接种KM小鼠皮下毒性最小 ;接种DBA 2、C57BL 6、6 15小鼠腹腔毒性较大 ,致死性高 ,对BALB c和KM小鼠的致死性弱 ;E2G8瘤细胞在KM和 4种纯系小鼠皮下均能很好生长肿瘤 ,其中在KM小鼠皮下肿瘤生长最大 ,在BALB c小鼠皮下肿瘤最小 ;KM、C57BL 6、6 15、DBA 2、BALB c小鼠皮下接种瘤细胞第 12天瘤重分别为 (2 4 0± 1 30 ) ,(0 90± 0 4 8) ,(1 2 0± 0 38) ,(1 10± 0 2 9) ,(0 80± 0 30 )g ;E2G8细胞接种 5个不同品种 (系 )小鼠制备的肿瘤模型 ,用CTX治疗 ,抑瘤率由高到低依次为6 6 7% (6 15 ) ,5 5 0 % (BALB c) ,5 3 3% (C57BL 6 ) ,5 0 % (KM) ,36 4 (DBA 2 ) ,其中 6 15小鼠建立的模型对CTX的治疗最敏感。结论　E2G8细胞株接种 5个不同品种 (系 )小鼠 ,所测生物学特性不完全相同 ,但是从腹腔 皮下接种、CTX     

两种玻璃化胚胎冷冻方法对不同品系小鼠胚胎冷冻效果比较

目的探讨EFS和DAP两种玻璃化冷冻方法对不同品系小鼠胚胎冷冻的效果。方法6个品系小鼠（KM、ICR、BALB／c、C57BL／6J、OB／OB、LAP／~TAOF59）的2-cell胚胎分别用EFS和DAP两种玻璃化冷冻方法进行冷冻和复苏,比较两种冷冻方法的胚胎复苏率和着床率。结果6个品系小鼠冷冻胚胎EFS方法的平均复苏率为69．97％（47．9％～83．6％）,DAP方法的平均复苏率47．23％（26．3％-76．7％）,EFS方法明显优于DAP方法。其中KM、ICR和BALB／c小鼠EFS方法的冷冻复苏率显著高于DAP方法（P〈0．01）;冻融胚胎移植后EFS方法的平均着床率27．23％（1．75％一45．0％）,DAP方法的平均着床率31．43％（7．0％一46．3％）。除KM、ICR小鼠外,其他4个品系小鼠的着床率DAP方法高于EFS方法。结论KM和ICR远交群小鼠胚胎适合用EFS方法冷冻保存;C57BL／6J、OB／OB、LAP／aTAOF59三个品系小鼠DAP方法优于EFS方法,但差异不大;BALB／c小鼠两种玻璃化冷冻方法的冻融胚胎着床率均较低,需进一步研究。     

近交系小鼠移植性肝癌模型建立及对比分析

目的：通过对比分析选择建立原位移植性肝癌模型的最佳小鼠品系。方法选取C57、C3H和BALB／c各10只小鼠分别作为模型组Ⅰ、模型组Ⅱ和模型组Ⅲ,沿腹中线开腹后将H22细胞接种到各模型组小鼠肝脏实质内。于注射后第15天剖腹探查,观察各组成瘤率,测量腹水量和肿瘤体积,并进行肿瘤病理学分析。结果三组小鼠存活率均为100％,15天后三组小鼠均产生腹水,但三组腹水量之间不具有统计学差异。模型组Ⅰ小鼠肝癌移植成功率为100％,高于模型组Ⅱ的60％和模型组Ⅲ的30％。模型组Ⅰ小鼠肝脏肿瘤全部为大块紧实灰白色病灶,其肿瘤平均体积显著大于模型组Ⅱ和模型组Ⅲ（ P＜0.05）。病理结果证实三组小鼠肝脏的灰白色病灶均为原位肝细胞癌。结论 C57小鼠是复制原位移植性肝癌模型较为理想的实验动物,为今后研究原位肝癌的发病机制提供良好的实验平台。     

甲型H1N1流感病毒感染不同免疫缺陷小鼠的比较

目的宿主免疫系统的功能状态在病毒的感染中起着至关重要的作用,本实验观察了不同免疫缺陷小鼠感染甲型H1N1流感病毒的差异。方法使用六个品系的近交系小鼠,经乙醚麻醉后进行滴鼻攻毒,分析其在病毒感染后存活率、体重变化和肺组织病理改变的异同。结果感染H1N1病毒的6种小鼠在观察的14d内,野生型的C57BL／6小鼠感染开始体重缓慢下降,感染后期有所回升,有半数存活;BALB／c小鼠和四种免疫缺陷品系小鼠感染病毒后体重随病情发展快速下降,死亡率均为100％。野生型C57BL／6小鼠感染初期为较弥漫的间质性肺炎,后期病变逐渐局限;BALB／c小鼠和四种免疫缺陷品系小鼠感染病毒后出现弥漫的中重度间质性肺炎,细支气管上皮有变性坏死,但炎症细胞明显少于C57BL／6小鼠。结论在甲型H1N1流感病毒的初次感染中固有免疫和特异性免疫分别在感染的初期和后期起主要作用,宿主免疫系统的功能状态影响着甲型H1N1病毒感染和预后。     

小鼠Lewis肺癌不同部位皮下移植瘤模型的比较

目的探究不同部位肺癌皮下移植瘤存在的差异,为肺癌研究者提供提供基础依据。方法将稳定表达虫萤光素酶的小鼠Lewis肺腺癌细胞(ll2-luc-m38)分别注射于C57 BL/6小鼠的右腋皮下、右腹股沟皮下、脚垫皮下,定期利用小动物活体成像系统观察小鼠皮下移植瘤成瘤情况及转移情况,观察不同部位荷瘤小鼠的生存时间和死亡率,肿瘤组织取材,采用石蜡包埋、切片、HE染色做出病理学诊断。并将小鼠处死后立即进行肺部组织固定、观察转移灶。对皮下移植瘤行切除术观察小鼠术后生存情况和转移情况。结果腋下组和腹股沟组成瘤时间较早,成瘤率为100%,脚垫组成瘤时间较晚,成瘤率为33%;腹股沟组和腋下组瘤体积增长迅速,其中腹股沟组瘤体积增长最快;接种后第21天腋下组70%的小鼠出现了肺转移,转移灶数目较多;腹股沟组50%小鼠出现肺转移,且转移灶数目较少;脚垫组小鼠未观察到肺转移灶。脚垫组小鼠死亡率最高。腹股沟组和腋下组小鼠可行皮下移植瘤切除术,术后存活率为100%。结论小鼠lewis肺癌皮下移植瘤模型中,腹股沟组和腋下组成瘤率高,可耐受移植瘤切除术,手术死亡风险低,便于监测,操作简单且可重复性高,其中腋下组转移性更好。     

IRM-2小鼠移植性肿瘤模型的生物学特性

目的观察IRM-2小鼠和C57BL/6小鼠接种Lewis肺癌生物学特性的对比研究。方法取肿瘤组织研磨,用生理盐水稀释成2×10^6/mL,取细胞悬液接种于IRM-2小鼠和C57BL/6小鼠腋下,0.2 mL/只。观察两品系肿瘤生长、荷瘤鼠生存时间,外周血细胞及病理指标变化。结果两品系小鼠成瘤率均是100%,荷瘤鼠存活时间无明显差异,IRM-2小鼠荷瘤鼠体重净增长明显高于C57BL/6荷瘤小鼠（P〈0.05）。白细胞分类及病理指标变化无明显差别。结论IRM-2小鼠与C57BL/6小鼠Lewis肺癌模型生物学特性基本一致,IRM-2小鼠可以建立稳定的Lewis肺癌肿瘤模型应用于实验研究。     

4种小鼠的寒、热体质研究

[目的]研究4种品系小鼠的寒、热体质。[方法]8~9周龄昆明、BALB/c、C57BL/6J、ICR小鼠,以及4~5周龄昆明小鼠,同步系统检测其生物学特性,然后以统一的评价标准评价4种品系小鼠的寒、热体质。并对BALB/c小鼠给予参桂理中丸和利血平做药物反证。[结果]①4~5周龄昆明小鼠与8~9周龄昆明小鼠比较体质明显偏热;②BALB/c小鼠与C57BL/6J小鼠比较体质偏寒;③8~9周龄雄性BALB/c小鼠、雄性和雌性C57BL/6J小鼠与8~9周龄相应性别昆明小鼠比较体质无明显差异;8~9周龄雌性BALB/c小鼠与8~9周龄雌性昆明小鼠比较体质偏寒;④8~9周龄ICR小鼠与8~9周龄BALB/c小鼠、C57BL/6J小鼠比较体质偏热;8~9周龄雄性ICR小鼠与8~9周龄雄性昆明小鼠比较体质偏热。[结论]4种品系小鼠存在寒、热体质差异。     

5个品系小鼠胚胎干细胞系建立的方法学比较

以70％的大鼠心脏细胞条件培养基(RH-CM)为培养液,以小鼠胚胎成纤维细胞(PMEF)为饲养层,采用添加1％鸡血清的消化液和“连续离散法”作为小鼠Es细胞建系的改进方法,比较了5个品系小鼠ES细胞系建立的特点。与常规方法相比,3个近交系小鼠129／ter、C57BL/6J、BALB／c的ES细胞建系率分别由11．8％、3．7％和2．9％提高到33．3％、13．3％和19．4％,差异十分显著;直接采用改进的方法建立KM和ICR小鼠ES细胞系,建系率分别达12％和42．1％。讨论了ICM增殖的时间,即离散时机对ES集落形成及建系率的影响,结果显示：129／ter、C57BL/6J、BALB／c、KM和ICR小鼠品系ICM适宜的离散时机分别为增殖4～6d、3～3．5d、4d、4～5d和4～5d;同时,讨论了不同ES细胞建系所需最适宜的消化液浓度,其中BALB／c小鼠的ES细胞对高浓度的消化液十分敏感,0．05％Trypsin-0．008％EDTA是其比较理想的离散浓度。设计了两种离散方法,即“一次离散法”和“连续离散法”,用来离散增殖的ICM和ICM离散后出现的ES集落,结果表明：后者在建系过程中的作用明显优于前者。RH-CM与添加uF的常规ES细胞培养基相比,不但具有显著抑制小鼠ES细胞分化、维持其二倍体核型的作用,而且明显促进ES细胞的贴壁生长。新建细胞系鉴定结果表明,这一改进方法有效地维持了其作为多能性胚胎干细胞的一系列特征。     

MBP-特异性T细胞的生物学性状分析

目的：在C57BL／6小鼠建立MBP－特异性T细胞系,并探讨其生物学特性。方法：取MBP免疫的C57BL／6小鼠腹股间淋巴结的淋巴细胞在体外培养,用MBP及同系小鼠的脾细胞反复刺激,建立了MBP－特异性T淋巴细胞。以流式细胞仪检测其细胞表面标志,以ELISA双抗体夹心法检测MBP－特异性T细胞产生的IFN－γ及IL－4水平。结果：CD4^ T细胞占90％以上。MBP－特异性T细胞主要产生IFN－γ。结论：该T细胞系为CD4^ 、Th1类淋巴细胞;在C57BL／6小鼠体内存在能识别MBP的自身反应性T细胞。     

不同品系小鼠在三种常见抑郁检测方法中的行为学表现

目的探讨4种不同品系小鼠在3种实验（空场实验、悬尾实验及强迫游泳实验）中的行为学差异,为抗抑郁新药研究中的实验动物选择提供参考。方法利用空场实验检测C57BL/6、BALB/c、ICR、和昆明小鼠的自主活动能力和对新奇环境的探索能力;利用悬尾实验和强迫游泳实验检测它们在应激刺激下的行为绝望状态。结果在空场实验中,BALB/c、ICR和昆明小鼠的运动总路程、运动速度和运动时间明显高于C57BL/6小鼠（P〈0.05）,ICR和昆明小鼠的直立次数也明显高于C57BL/6小鼠（P〈0.05）;悬尾实验C57BL/6小鼠的不动时间显著长于其他3种品系小鼠（P〈0.05）,但是4种品系小鼠在强迫游泳实验中的不动时间差异无显著性。结论 C57BL/6小鼠自发活动量低,对新奇环境的探索能力差,并且在急性应激刺激下容易造成行为绝望,因此C57BL/6小鼠可能适合作为急性应激抑郁模型动物。     

不同品系小鼠对实验感染念珠状链杆菌敏感性的观察

本文通过念珠状链杆菌（Ｓｔｒｅｐｔｏｂａｃｉｌｕｓｍｏｎｉｌｉｆｏｒｍｉｓ,Ｓ．ｍ．）实验感染昆明、Ｃ５７ＢＬ／６Ｊ、ＢＡＬＢ／ｃ、ＩＣＲ、ＮＩＨ、ＤＢＡ共６个品系小鼠,观察其对Ｓ．ｍ．敏感性的差异。其中昆明、Ｃ５７ＢＬ／６Ｊ两个品系在腹腔接种后表现出明显的临床、病理改变。昆明小鼠发病率和死亡率分别为９２％和８０％;Ｃ５７ＢＬ／６Ｊ分别是８０％和１２％。昆明小鼠较之Ｃ５７ＢＬ／６Ｊ小鼠起病急、病情严重,多数动物死于感染的急性期。其余品系的发病率为：ＮＩＨ８％、ＢＡＬＢ／ｃ和ＤＢＡ４％,没有动物死亡;ＩＣＲ在接种后无任何临床病理改变。在实验感染后临床病理改变方面,昆明小鼠和Ｃ５７ＢＬ／６Ｊ小鼠间有较大不同。昆明小鼠以末梢血管淤血、四肢尾部水肿、关节炎、截瘫、腹泻为主,而Ｃ５７ＢＬ／６Ｊ小鼠则以注射部位和其它部位皮下脓肿、化脓性关节炎为主。本研究提示,中国昆明小鼠对Ｓ．ｍ．敏感性最高,可以将其作为“哨兵动物”用于实验大鼠Ｓ．ｍ．的常规监测;不同品系小鼠不仅对实验感染Ｓ．ｍ．的敏感性不同,而且表现出不同的临床病理改变。     

Leishmania major: analysis of lymphocyte and macrophage cellular phenotypes during infection of susceptible and resistant mice

Genetically susceptible BALB/c and resistant C57BL/6 mice were infected with Leishmania major and the phenotypes of the responding cells in the draining lymph nodes and cutaneous lesions were analyzed. As early as 1 week, significantly increased numbers of L3T4+ cells as compared to Lyt-2+ cells were present in BALB/c mice lymph nodes (P less than 0.005). Increases in L3T4+ and Lyt-2+ cells were comparable in C57BL/6 mice, resulting in threefold lower L3T4/Lyt-2 ratio than in BALB/c mice. T cell subsets were activated in both strains to express interleukin-2 receptor (IL2R) above resting values, although greater numbers of activated L3T4+ cells were present in the draining lymph nodes from BALB/c at 1 and 3 weeks of infection than in C57BL/6 (P = 0.02). Despite the presence of activated L3T4+ cells in both strains, macrophages differed in the expression of immunologically important surface molecules during infection. Tissue macrophages from BALB/c mice were IgG1/G2b Fc receptor (FcR)+ and Ia- late in disease, whereas macrophages in C57BL/6 became FcR and Ia during healing. BALB/c mice, treated with monoclonal antibody GK1.5 to transiently deplete L3T4+ cells, became resistant to subsequent infection and developed a macrophage phenotype that was FcR- and Ia+. These differences in macrophage phenotype were closely linked to susceptibility during infection with L. major and may play a role in the pathophysiology of murine leishmaniasis.     

禽流感H5N1亚型病毒对五个不同品系小鼠致病性的比较(英文)

目的比较了不同遗传背景小鼠对禽流感H5N1亚型病毒的致病敏感性,为H5N1禽流感模型制作和机理研究提供依据。方法近交系BALB/c、C57BL/6和封闭群ICR、NIHSwiss和KMSwiss共五个不同品系小鼠。每个品系实验动物30只,分接毒组20只,空白对照组10只,每组雌雄各半。病毒株为A/Goose/Guangdong/NH/2003(H5N1),经测定TCID50为10-4.875/mL。接毒组通过鼻腔接种0.1mL病毒液,对照组接种正常鸡胚尿囊液。小鼠接毒后连续观察14d,观察记录临床症状、体温、体重变化,对在实验期间死亡和实验14d结束后仍然存活的小鼠均进行组织器官病理取材,进行RT-PCR病毒分离检测、HE染色及H5N1抗原特异性免疫组化染色。结果①临床症状:H5N1禽流感病毒能感染五个品系的小鼠,引起呼吸急促等症状和一过性体重、体温下降。②死亡情况:小鼠在接毒后第1天即出现死亡,死亡的高峰期集中在接毒后第3～6天。五个品系小鼠死亡率存在差异,BALB/c为70%,ICR为50%,NIHSwiss为40%,C57BL/6为25%,KMSwiss为10%;③病毒分离:各组接毒小鼠在死亡后均进行了病毒分离,死亡小鼠的肺脏均分离到病毒,其他脏器未分离到病毒。④病理变化:实验期间五个品系死亡小鼠肺脏病理改变相近。大体观:死亡小鼠肺部淤血,呈暗红色,体积增大,局部肺组织实变。镜下观:死亡小鼠的共同病理改变为间质性肺炎,具体表现为肺泡腔及间质出血、炎性细胞浸润;间质增生,肺泡隔增宽;肺泡腔中见纤维素性渗出,透明膜形成。⑤免疫组化结果 :在死亡小鼠的气管上皮细胞和肺巨噬细胞可观察到H5N1禽流感病毒阳性表达。结论小鼠作为H5N1禽流感病毒模型具有普适性,不同品系小鼠感染鹅源H5N1禽流感病毒的临床症状、病程和病理变化与人禽流感病例相似。不同品系小鼠的死亡比例有明显差别,可以根据不同的实验目的 ,选择不同品系的小鼠制作H5N1禽流感动物模型。不同品系的遗传特性对禽流感易感性产生明显的影响,遗传背景可能与H5N1禽流感病毒感染应答机理存在联系:BALB/c和C57BL/6均为近交系,其中BALB/c小鼠的品系特征之一表现为干扰素产量低,接种H5N1病毒后表现为高死亡率(70%),而C57BL/6小鼠的干扰素产量高,接种H5N1病毒后表现为低死亡率(25%),提示不同遗传背景小鼠的干扰素水平与H5N1感染致死具相关性。为进一步研究H5N1禽流感病毒易感性相关基因以及其与宿主免疫反应的关系提供了一个研究基础。     

念珠状链杆菌在小鼠群中的自然感染和发病特征的观察

本文在国内首次报告了念珠状链杆菌在清洁级Ｃ５７ＢＬ／６Ｊ小鼠群中的自然感染,并从临床、病理解剖、病原学及流行病学方面进行了较为详细的观察,在受检的１４例发病动物中,颈部淋巴结肿大、化脓占７１．４％,皮下、肺门淋巴结脓肿分别占５０．０％和２１．４％,多发性关节炎（包括趾、跗关节）占２１．４％,子宫积脓占７．１％,从所有病灶及部分动物的血液、脾、肝、肺、肾均分离到了单一的细菌。该菌在小鼠成功地进行了急性感染实验,受感染动物出现了典型的念珠状链杆菌病的临床及病理特征,即败血症、关节炎、淤血、水肿、紫绀、结膜炎等。所分离的致病菌在病原学上也完全符合念珠状链杆菌的病原学特征。在饲养环境上与发病鼠群有密切关系的其它４个品系小鼠群,即６１５、ＢＡＬＢ／ｃ、ＣＢＡ、ＫＭ,均未波感染,证明在对该菌的易感性方面存在品系差异。     

Changes in the precursor frequencies of IL-4 and IFN-gamma secreting CD4+ cells correlate with resolution of lesions in murine cutaneous leishmaniasis.

Limiting dilution analysis was used to estimate the frequency of clonogenic Ag-specific CD4+ T lymphocytes in draining lymph nodes of mice over the course of infection with Leishmania major, and to measure the production of IL-2, IL-3, IL-4, IFN-gamma, and TNF by the resultant clones. Infection of both genetically susceptible BALB/c ("non-healer") and resistant C57BL/6 ("healer") mice resulted in at least a fourfold increase in the frequency (to about 0.3%) and at least a 10-fold increase in the total number of lymph node CD4+ cells that formed clones when cultured with L. major Ag in vitro. At 1 wk after infection, the majority of clones from BALB/c mice secreted IL-4 (precursor frequency 0.15%) and fewer secreted IFN-gamma (0.05%); this pattern remained constant for at least 8 wk after infection. In C57BL/6 mice, however, a high precursor frequency of IL-4-secreting clones was measured in the first 1 to 2 wk when the mice had lesions, but resolution of infection was associated with a decrease in the frequency of IL-4-secreting clones (from 0.13% at 2 wk to 0.03% at 4 wk) and an increase in the frequency of IFN-gamma-secreting clones (from 0.08% to 0.22%). At all stages of infection, most clones from either mouse strain secreted IL-3 and very few secreted TNF. Analysis of PCR-amplified cDNA from draining lymph nodes of infected mice also revealed that IL-4 and IFN-gamma mRNA were expressed in both mouse strains early in infection. IL-4 mRNA was the major species at 2 and 6 wk after infection in BALB/c mice, but declined relative to IFN-gamma mRNA over this time in C57BL/6 lymph nodes. Precursor frequency estimates of lymphokine-secreting CD4+ cells in draining lymph nodes therefore correlated with lymphokine expression patterns in vivo. Analysis of a panel of individual short term clones derived from mice 1 wk after infection revealed marked heterogeneity in lymphokine production patterns. In BALB/c mice, 49% secreted IL-4 without IFN-gamma, 18% secreted IFN-gamma without IL-4, and 14% secreted both IL-4 and IFN-gamma. Similarly in C57BL/6 mice, 39% secreted IL-4, 20% secreted IFN-gamma, and 17% secreted both lymphokines. Many of the clones also produced IL-3 and/or IL-2. Together the data suggest that both IL-4 and IFN-gamma are synthesized early in infection of susceptible and resistant mice as assessed by mRNA and precursor frequency analyses.(ABSTRACT TRUNCATED AT 400 WORDS)     

T cells from Leishmania major-susceptible BALB/c mice have a defect in efficiently up-regulating CXCR3 upon activation

Genetic background influences the outcome of Leishmania major infection. C57BL/6 mice mount a Th1 response and resolve infection. In contrast, BALB/c mice mount a Th2 response and develop chronic lesions. This susceptible phenotype is seen even though BALB/c mice generate IFN-gamma-producing T cells at proportions similar to C57BL/6 mice in their lymph nodes (LN) early after infection. We had previously shown that chemokine receptor CXCR3 mediates immunity against L. major by recruiting IFN-gamma-producing T cells to the lesions of C57BL/6 mice. Therefore, we hypothesized that IFN-gamma-secreting T cells in BALB/c mice are unable to confer protection because they may be defective in up-regulating CXCR3. To test this hypothesis, we analyzed kinetics of CXCR3-expressing T cells in the LN and lesions of BALB/c and C57BL/6 mice during L. major infection. Additionally, we compared the ability of T cells from BALB/c and C57BL/6 mice to up-regulate CXCR3 upon activation. We found that resolution of L. major infection in C57BL/6 mice was associated with an increase in the proportion of CXCR3(+) T cells in regional LN and lesions, whereas disease progression in BALB/c mice was associated with a decrease in these populations. Anti-CD3/CD28-activated T cells from naive BALB/c but not C57BL/6 mice were defective in up-regulating CXCR3. Impaired induction of CXCR3 on BALB/c T cells was not due to lack of IFN-gamma and was mediated partially by IL-10 but not IL-4 or IL-13. We propose that defective CXCR3 up-regulation on T cells in BALB/c mice may contribute to L. major susceptibility.     

Studies on the induction of tolerance to alloantigens. II. The generation of serum factor(s) able to transfer alloantigen-specific tolerance for delayed-type hypersensitivity by portal venous inoculation with allogeneic cells

The administration of C3H/He spleen cells into allogeneic BALB/c mice via portal venous (p.v.) route resulted in C3H/He alloantigen-specific tolerance for delayed-type hypersensitivity (DTH) responses. When serum from these tolerant BALB/c mice were transferred into naive syngeneic BALB/c mice, the recipient mice lost the capability of generating DTH responses as induced by s.c. immunization with C3H/He cells. Tolerance was transferred only by serum from BALB/c mice inoculated p.v. with C3H/He cells, but not by serum from C3H/He mice inoculated p.v. with C3H/He cells, or BALB/c mice inoculated i.v. with C3H/He cells. This tolerogenic activity in serum from p.v. inoculated BALB/c mice was C3H/He alloantigen specific, because the transfer of the serum did not interfere with the development of anti-C57BL/6 DTH responses in recipient BALB/c mice. Such a serum factor(s) was inducible as early as 1 wk after the inoculation of C3H/He cells into BALB/c mice and not associated with anti-C3H/He alloantibody activity. Moreover, anti-C3H/He or C57BL/6-specific tolerogenic factor(s) prepared in the respective BALB/c or C3H/He mice was successfully transferred into totally allogeneic recipient mice, indicating no requirement of H-2, as well as non-H-2 restriction for the function of serum tolerogenic factor(s). Thus this study demonstrates that p.v. inoculation of allogeneic cells generates serum factor(s) able to transfer in H-2 and non-H-2-unrestricted manners the in vivo tolerance of the alloreactivity specific for alloantigens used for p.v. inoculation.     

Comparative analysis of clinics,pathologies and immune responses in BALB/c and C57BL/6 mice infected with Streptobacillus moniliformis

Streptobacillus (S.) moniliformis is a rat-associated zoonotic pathogen that occasionally causes disease in other species. We investigated the working hypothesis that intranasal infection might lead to different immune responses in C57BL/6 and BALB/c mice associated with distinct pathologies. This study confirmed with 75% mortality the known high susceptibility of C57BL/6 mice to Streptobacillus moniliformis infection in comparison to BALB/c mice which did not develop signs of disease. Main pathologies in C57BL/6 mice were purulent to necrotizing lymphadenitis and pneumonia. Significant seroconversion was recorded in surviving mice of both strains. Differentiation of IgG-subclasses revealed mean ratios of IgG2b to IgG1 below 0.5 in sera of all mice prior to infection and of BALB/c mice post infection. In contrast, C57BL/6 mice had a mean IgG2b/IgG1 ratio of 2.5 post infection indicating a Th1 immune response in C57BL/6 versus a Th2 response in BALB/c mice. Evaluation of different sentinel systems revealed that cultural and serological investigations of these animals might not be sufficient to detect infection. In summary, an intranasal S. moniliformis infection model in C57BL/6 mice leading to purulent to necrotizing inflammations in the lung, the lymph nodes and other organs associated with a Th1 immune response is described.     

In vitro splenic T cell responses of diverse mouse genotypes after oronasal exposure to mouse hepatitis virus, strain JHM.

Mortality rates among BALB/cByJ, A/JCr, C3H/HeSnJ, and C57BL/6NCr mice inoculated oronasally with mouse hepatitis virus (MHV) strain JHM, ranged from 25 to 67%. Spleen cells harvested from the first three genotypes at 5 days postinoculation proliferated poorly in response to concanavalin A stimulation and produced significantly less interleukin (IL) 2 than cells from uninfected control mice. The function of spleen cells harvested at 14 days postinoculation varied and was host genotype-dependent. Despite clinical signs among some infected C57BL/6NCr mice, spleen cell function was relatively unaffected. C57BL/10ScNCr, B10.A, and SJL/JCr mice remained clinically normal after MHV inoculation. Proliferation and IL2 production by cells from inoculated C57BL/10ScNCr and B10.A mice were similar to responses of their respective controls. In contrast, cells from inoculated SJL/JCr mice were hyper-responsive and produced peak levels of IL2 earlier than control cells. Among the seven genotypes tested, only BALB/cByJ and C3H/HeSnJ spleen cells produced detectable IL4 after primary stimulation with concanavalin A or after priming and restimulation. Primary IL4 production by cells from these two genotypes was significantly reduced if donors were inoculated with MHV 5 days prior to spleen harvest. IL4 production by cells from acutely infected BALB/cByJ mice was considerably enhanced by priming and restimulation.