Listr1遗传位点影响小鼠对约氏疟原虫易感性的研究

探讨Listr1遗传位点影响小鼠对疟原虫易感性的可能性及其初步作用机制。致死型约氏疟原虫(Plasmodiumyoelii17XL,P.y17XL)感染C.B6By-Listr1小鼠(BALB/c小鼠基因背景下引入C57BL/6小鼠Lis-tr1遗传位点的同类系小鼠)和BALB/c小鼠,分析二者生存率和感染率的差异;HE染色分析P.y17XL感染后第5天C.B6By-Listr1小鼠和BALB/c小鼠肝脏组织损伤情况;定量PCR法检测P.y17XL感染后小鼠肝脏组织第1、2、5天IL-1β、IL-6、TNF-α、IFN-γ的表达含量。结果显示,P.y17XL感染后4~8dC.B6By-Listr1小鼠虫血症水平显著高于BALB/c小鼠(P<0.05)。C.B6By-Listr1小鼠于感染后7~9d全部死亡;而半数BALB/c小鼠于感染后8~9d死亡,其余BALB/c小鼠至感染后第13天仍存活,两种小鼠生存率差异具有统计学意义(P<0.01)。C.B6By-Listr1小鼠P.y17XL感染后第5天肝组织HE染色可见到明显的疟色素沉积;而BALB/c小鼠全片基本未见到疟色素的沉积。P.y17XL感染后第2天BALB/c小鼠肝组织IL-6(P<0.05)、TNF-α(P<0.05)mRNA水平显著高于C.B6By-Listr1小鼠。结果表明Listr1遗传位点可以影响小鼠对疟原虫的易感性,与肝脏固有免疫相关。     

伯氏疟原虫红内期发育周期观察

伯氏疟原虫是目前广泛应用的实验动物疟原虫种株,因此了解其生物学特性十分重要。本文观察了该原虫红内期发育周期的同步性和规律性,并比较了在近交系BALB/C小鼠和远交系昆明小鼠体内的发育情况。一、材料与方法(一)动物:近交系BALB/C小鼠和远交系昆明小鼠各三只,15～20克,本校实验动物部提供。(二)虫种:伯氏疟原虫(Plasmodium berghei)NK株,由中国军事医学科学院提供,经本实验室血传转种和冰冻保存一年左右。(三)动物接种:按Tosta(1980)的方法用Percoll密度梯度离心分离原虫,取Percoll浓度为60%与65%交界层细胞(成熟滋养体占全部原…     

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。     

CBA、BALB／c、C57BL、昆明系小鼠及豚鼠听性脑干反应阈值的检测

目的:比较CBA、BALB/c、C57BL、昆明系小鼠及豚鼠5种啮齿类动物的正常听性脑干反应(ABR)的阈值及其频率特性.方法:采用IHS SmartEP 3.91系统对4种小鼠和豚鼠的ABR进行检测和比较,使用短音(Tone-pip)作为刺激声测定其各频率的阈值及其特点,绘制各自的听觉频率-阈值的关系曲线,找出各自的最佳刺激频率.结果:五种啮齿类动物中,豚鼠的ABR阈值最低,然后依次是昆明系小鼠,CBA小鼠,BALB/c小鼠,C57BL小鼠;其ABR最佳反应阈值均为10 kHz,即在10 kHz时各自的ABR阈值最低;频率低于10 kHz时,其ABR阈值逐渐升高,高于10 kHz时,ABR阈值逐渐降低,这是五种被检测动物ABR频率-阈值的关系曲线的共同特点.结论:实验所检测的五种啮齿类动物中,豚鼠的听觉功能最好:在4种小鼠中,昆明系小鼠的听觉功能较其余小鼠的为好;这五种啮齿类动物的听觉最适刺激频率均为10 kHz,最适合的测试频率范围是8 kHz至24 kHz.     

柯萨奇病毒B3型诱导的免疫偏离与心肌炎发病关系的研究

目的 研究2种近交系小鼠在柯萨奇病毒B3型(CVB3)感染后辅助性T细胞(Th)免疫偏离对心肌炎发病的影响。方法 用CVB3腹腔感染BALB/c和C57BL/62种近交系小鼠,感染后7d通过检测小鼠血清肌酸激酶(CK)活性,观察心脏外观变化以及心脏石蜡切片H.E染色观察心脏病理改变,比较2种小鼠心肌炎的发病情况;通过体外感染心肌细胞观察病毒复制情况以及体内心脏组织病毒载量的分析,比较2种小鼠对病毒感染和复制的差异;通过检测感染小鼠细胞因子白细胞介素-4(IL-4)、IL-12和γ干扰素(IFN-γ)的表达,抗CVB3VP1抗体的亚型以及T-bet和Gata-3的表达,比较2种小鼠Th免疫偏离的情况。结果 CVB3在体外和体内都可以感染BALB/c和C57BL/6小鼠心肌细胞,但仅BALB/c小鼠感染后可发生明显的病毒性心肌炎,C57BL/6小鼠则不能;BALB/c小鼠感染后表现为Th1型免疫反应而C57BL/6小鼠则偏向于Th2型免疫反应。结论 CVB3感染2种品系小鼠表现为不同的心肌炎发生率,与其诱导了不同类型的免疫偏离密切相关。     

具有临床代表性的艰难梭菌感染小鼠稳定模型的构建

目的构建临床代表性好、稳定性佳的艰难梭菌感染小鼠模型,为艰难梭菌感染相关疾病提供研究工具。方法选择C57BL/6、BALB/c、昆明小鼠,经抗生素诱导后,分别予以不同浓度(108 CFU/mL~10~(10) CFU/mL)的临床分离菌株混悬液灌胃,观察不同品系小鼠不同时间点腹泻、全身情况及结肠组织病理学变化。结果灌菌后,BALB/c小鼠10~(10) CFU/mL浓度组全部出现腹泻,死亡率为16.7%;其他实验组小鼠腹泻程度差异较大或仅部分出现轻度腹泻。腹泻小鼠表现为稀烂便甚至水样便和湿尾现象,体重减轻,肠道病理显示结肠黏膜充血水肿伴炎性细胞浸润。结论经5种抗生素灌胃9d+克林霉素腹腔注射诱导,10~(10) CFU/mL艰难梭菌活菌混悬液灌胃后构建的BALB/c小鼠艰难梭菌感染模型最稳定。     

A型流感病毒感染BALB/c小鼠炎症模型的建立

目的用小鼠炎症动物模型分析A型流感病毒的致病性。方法三株不同的A型流感病毒A/swine/Jiangsu/C1/08 (H9N2)(H9C1)、A/swine/Shandong/731/2009 (SD731)、A/Puerto Rico/8/34 (H1N1)(PR8),以1×10~6 TCID_(50)经鼻感染5周龄BALB/c小鼠,观测临床症状,检测肺组织的病毒载量和炎症因子水平。结果 BALB/c小鼠致病性实验中,SD731和PR8病毒引起的肺组织的炎症反应水平及病毒的复制显著高于H9C1,SD731致死率为80%,PR8为100%;H9C1病毒感染伴随着体重的减轻,但小鼠无死亡。结论成功建立了流感病毒感染小鼠的炎症模型。     

一种新的近交系实验动物遗传监测方法及小鼠性别相关RAPD标记的发现

我们用21个10 bp的随机短引物对来自昆明、成都、上海、北京四个地方的BALB/c小鼠以及C57BL小鼠、昆明种小白鼠进行了随机扩增多态DNA(RAPD)分析,发现13个引物的扩增产物在BALB/c小鼠和C 57 BL小鼠中有差异,8个引物的扩增产物在BALB/c小鼠和昆明种小白鼠之间不同.在四个地方的BALB/c小鼠中,成都、上海、北京的BALB/c小鼠其遗传背景均一,而来自昆明的BALB/c小鼠中,有2只的4个引物的扩增产物不同于其它的BALB/c小鼠,表明这两只BALB/c小鼠可能曾发生过某种程度的遗传改变或污染。实验结果显示RAPD方法是一种有效的近交系实验动物遗传监测手段。实验中一个有趣的结果是,在OPG 2、OPE 4、OPE 9的扩增产物中,发现了严格的性别依赖的PAPD标记。OPE 9扩增产物中,凡雄性个体都有一条0.88 kb的标记.OPG 2、OPE 4则在所有的雄性个体中多扩增出一条约1.2 kb的带。通过交叉PCR扩增和斑点杂交证明OPG 2、OPE 4 得到的雄性特异性RAPD标记虽分子大小一致,但不具同源性。这些性别相关RAPD标记的染色体定位和性质分析正在进一步进行中.     

遗传位点影响小鼠对约氏疟原虫易感性的研究

探讨Listr1遗传位点影响小鼠对疟原虫易感性的可能性及其初步作用机制。致死型约氏疟原虫(Plasmodium yoelii 17XL,P.y17XL)感染C.B6By Listr1小鼠（BALB/c小鼠基因背景下引入C57BL/6小鼠Listr1遗传位点的同类系小鼠）和BALB/c小鼠,分析二者生存率和感染率的差异;HE染色分析P.y17XL感染后第5天C.B6By Listr1小鼠和BALB/c小鼠肝脏组织损伤情况;定量PCR法检测P.y17XL感染后小鼠肝脏组织第1、2、5天IL-1β、IL-6、TNF-α、IFN-γ的表达含量。结果显示,P.y17XL感染后4~8 d C.B6By Listr1小鼠虫血症水平显著高于BALB/c小鼠（P＜0.05）。C.B6By Listr1小鼠于感染后7~9 d全部死亡;而半数BALB/c小鼠于感染后8~9 d死亡,其余BALB/c小鼠至感染后第13天仍存活,两种小鼠生存率差异具有统计学意义（P＜0.01）。C.B6By Listr小鼠P.y17XL感染后第5天肝组织HE染色可见到明显的疟色素沉积;而BALB/c小鼠全片基本未见到疟色素的沉积。P.y17XL感染后第2天BALB/c小鼠肝组织IL-6（P＜0.05)、TNF-α（P＜0.05)mRNA水平显著高于C.B6By Listr1小鼠。结果表明Listr1遗传位点可以影响小鼠对疟原虫的易感性,与肝脏固有免疫相关。     

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。     

The impaired pregnancy outcome in murine congenital toxoplasmosis is associated with a pro-inflammatory immune response, but not correlated with decidual inducible nitric oxide synthase expression

Congenital toxoplasmosis is associated with adverse pregnancy outcome. Despite the type 1 immune response, C57BL/6 mice are more susceptible than BALB/c mice to Toxoplasma gondii infection. Additionally, successful pregnancy appears to be correlated with type 2 T helper maternal immunity and regulatory T cells. In order to investigate the mechanisms of susceptibility/resistance to congenital toxoplasmosis in mice with different genetic backgrounds and the influence of inducible nitric oxide synthase in pregnancy outcome, groups of C57BL/6, BALB/c and C57BL/6 iNOS(-/-) females were orally infected with T. gondii ME-49 strain on day 1 of pregnancy and were sacrificed on day 8 p.i. and day 19 p.i. The uterus and placenta were evaluated for the foetal resorption rate, parasite load, immunological and histological changes. C57BL/6 mice presented inflammatory foci in the decidua (endometrium) of the uterus at a higher frequency than BALB/c mice on day 8 p.i., and a large number of pregnant C57BL/6 mice presented necrotic implantation sites. The parasite was seldom found in the uterus or placenta of either lineage of mice. Interestingly, there was no observed difference in inducible nitric oxide synthase expression in the uterus and placenta of infected mice. In addition, higher levels of TNF-α were detected in serum samples from C57BL/6 mice compared with BALB/c mice. Accordingly, C57BL/6 mice presented with levels of 90% abortion compared with 50% in BALB/c mice on day 19 p.i. C57BL/6 iNOS(-/-) mice showed low placental parasite counts and high absorption rates, similar to wild type mice. The data suggest that the impaired pregnancy outcome due to T. gondii infection in C57BL/6 mice could be associated with a higher inflammatory response leading to cell apoptosis and necrosis of implantation sites compared with BALB/c mice, and this phenomenon was not due to inducible nitric oxide synthase expression in the decidua.     

Differences in interleukin-12 and -15 production by dendritic cells at the early stage of Listeria monocytogenes infection between BALB/c and C57 BL/6 mice

The mechanisms responsible for the resistance of C57BL/6 mice and for the susceptibility of BALB/c mice to infection with Listeria monocytogenes were studied by comparing early IL-12 and IL-15 production by dendritic cells (DC) after infection with L. monocytogenes. Splenic DC expressing CD11b(low) and CD11c(+) obtained from C57BL/6 mice at 3 and 6 h after L. monocytogenes infection expressed higher levels of IL-12 p40 mRNA and IL-12 p40 protein than did those from BALB/c mice. Concurrently, a larger amount of IFN-gamma was produced by the splenic T cells from C57BL/6 mice in response to immobilized anti-TCRalphabeta mAb than by those from BALB/c mice, while the splenic T cells from BALB/c mice produced a higher level of IL-4 upon TCR alphabeta stimulation than did those of C57BL/6 mice. IL-15 mRNA and intracellular IL-15 protein were detected more abundantly in the DC from C57BL/6 mice than in those from BALB/c mice on day 3 after infection. CD3(+) IL2Rbeta (+) cells in the spleen were increased in C57BL/6 mice but not in BALB/c mice at the early stage after infection. Furthermore, IL-12Rbeta2 gene expression was up-regulated in T cells from C57BL/6 mice but not in those from BALB/c mice at the early stage after listerial infection. These results suggest that the difference in early production of IL-12 and IL-15 by DC may at least partly underlie the difference in susceptibility to L. monocytogenes between C57BL/6 and BALB/c mice.     

Antibody-dependent cellular cytotoxicity and natural killer cytotoxicity of peritoneal cells from nude mice to herpes simplex virus-infected cells

Nude BALB/c mice (athymic) were more susceptible to fatal herpes simplex virus (HSV) than normal BALB/c mice (P = 0.002). The peritoneal cells of nude mice mediated levels of antibody-dependent cellular cytotoxicity (ADCC) of equal or greater magnitude than cells from normal BALB/c, heterozygote nu/+, or C57BL/6 mice. Unstimulated natural killer cytotoxicity of peritoneal cells from nude mice was higher (P less than 0.05) than that mediated by cells from C57BL/6 mice. Nude mice failed to make anti-HSV ADCC antibody 6 to 14 days post HSV inoculation, at times when nu/+, BALB/c, and C57BL/6 mice produced antibody. Passive reconstitution of nude mice with high titer intraperitoneal anti-HSV immune globulin provided circulating anti-HSV ADCC antibody and significant protection against lethal HSV infection.     

Effects of hypoxia on megakaryocyte size and number of C3H and BALB/c mice.

In an effort to explain the different platelet production capabilities of both normal and hypoxic male and female C3H and BALB/c mice, megakaryocyte size and number were determined utilizing bone marrow from both normal and hypoxic mice. The results indicate that normal BALB/c female mice have increased numbers of megakaryocytes, but of smaller size compared with either BALB/c male mice or to both sexes of C3H mice. An inverse relationship between the size and number of megakaryocytes was found in both normal and hypoxic mice; therefore, to evaluate total megakaryocyte characteristics, we calculated total megakaryocyte masses (TMM). With hypoxia, megakaryocyte number decreased, whereas megakaryocyte size increased. Despite the increase in megakaryocyte size, hypoxia caused a significant decrease in TMM (P less than 0.005) in all mice, but female C3H mice had higher TMM (P less than 0.05) than did female BALB/c mice. These data show that hypoxia decreases TMM in mice, and that the effect is greater in C3H mice than in BALB/c mice.     

In vitro immunomodulatory properties of osteogenic and adipogenic differentiated mesenchymal stem cells isolated from three inbred mouse strains

Mesenchymal stem cells (MSCs) are used for cell-based therapies because of their immunomodulatory properties. The immunomodulatory properties of adipogenic (AD) and osteogenic (OS) differentiated adipose tissue-derived MSCs (AD-MSCs) isolated from BALB/c, C57BL/6, and DBA mice were compared. Splenocytes proliferation was suppressed in the presence of AD-MSCs conditioned media in all mice. After OS differentiation, BALB/c AD-MSCs produced higher levels of TGF-β and IL-17 and lower levels of NO than AD-MSCs isolated from C57BL/6 and DBA mice. In addition, OS differentiated AD-MSCs isolated from DBA mice produced lower levels of IL-10 than AD-MSCs isolated from C57BL/6 and DBA mice. After in vitro AD and OD differentiation, AD-MSCs isolated from each mouse produced higher levels of NO and IDO than undifferentiated cells. Additionally, AD-MSCs isolated from C57BL/6 and DBA mice produced higher levels of NO than AD-MSCs isolated from BALB/c mice. Adipose tissue-derived MSCs thus retain their immunomodulatory properties after in vitro OS and AD differentiation in a strain-dependent manner.     

Host genetic background affects regulatory T-cell activity that influences the magnitude of cellular immune response against Mycobacterium tuberculosis

Using two mouse strains with different abilities to generate interferon (IFN)-γ production after Mycobacterium tuberculosis infection, we tested the hypothesis that the frequency and activity of regulatory T (Treg) cells are influenced by genetic background. Our results demonstrated that the suppressive activity of spleen Treg cells from infected or uninfected BALB/c mice was enhanced, inhibiting IFN-γ and interleukin (IL)-2 production. Infected C57BL/6 mice exhibited a decrease in the frequency of lung Treg cells and an increased ratio CD4(+):CD4(+)Foxp3(+) cells compared with infected BALB/c mice and uninfected C57BL/6 mice. Moreover, infected C57BL/6 mice also had a decrease in the immunosuppressive capacity of spleen Treg cells, higher lung IFN-γ and IL-17 production, and restricted the infection better than BALB/c mice. Adoptive transfer of BALB/c Treg cells into BALB/c mice induced an increase in bacterial colony-forming unit (CFU) counts. Furthermore, BALB/c mice treated with anti-CD25 antibody exhibited lung CFU counts significantly lower than mice treated with irrelevant antibody. Our results show that in BALB/c mice, the Treg cells have a stronger influence than that in C57BL/6 mice. These data suggest that BALB/c and C57BL/6 mice may use some different mechanisms to control M. tuberculosis infection. Therefore, the role of Treg cells should be explored during the development of immune modulators, both from the perspective of the pathogen and the host.     

Dysregulation of the inflammatory response to the parasite, Toxoplasma gondii, in P2X7 receptor-deficient mice

The P2X(7) receptor (P2X(7)R) is a two transmembrane receptor that is highly expressed on the surface of immune cells. Loss of function polymorphisms in this receptor have been linked to increased susceptibility to intracellular pathogens. P2X(7)R gene knockout (P2X(7)R(-/-); on a C57Bl/6J background), C57Bl/6J and BALB/c mice were infected with the avirulent ME49 strain of the intracellular parasite, Toxoplasma gondii, and susceptibility determined by monitoring weight loss. P2X(7)R(-/-) mice lost significantly more weight than C57Bl/6J mice from day 8p.i. C57Bl/6J, in turn, lost significantly more weight than BALB/c mice. Thus, by day 10p.i., P2X(7)R(-/-) mice had lost 5.7 ± 0.7% of their weight versus 2.4 ± 0.6% for C57Bl/6J mice, whereas BALB/c mice had gained 1.9 ± 0.5%; by day 12p.i., P2X(7)R(-/-) mice had lost 15.1±0.6%, C57Bl/6J had lost 10.1±0.8% and BALB/c had lost 4.8 ± 0.8% of their weight. Neither parasite burden nor liver pathology was greater in the P2X(7)R(-/-) mice than in C57Bl/6J mice but BALB/c mice had significantly smaller numbers of parasites and less pathology in their livers than these strains. Absence of the P2X(7) receptor did not affect IFN-γ, IL-12, IL-1β, monocyte chemoattractant protein-1 (MCP-1) or TNF production. However, both P2X(7)R(-/-) and C57Bl/6J mice produced more IL-1β and TNF than BALB/c mice. There was one important point of differentiation between the P2X(7)R(-/-) and C57Bl/6J mice, namely the significantly enhanced and prolonged production of nitric oxide, accompanied by delayed production of IL-10 in the P2X(7)R-deficient mice.     

Participation of embryonic genotype in the pregnancy block phenomenon in mice.

Pregnancy block by male pheromones in mice differs in incidence depending on the combination of strains. Female mice of BALB/cA strain mated with BALB/cA males show a 100% pregnancy block when exposed to males of inbred strain DDK shortly after copulation (Chung et al., Biol Reprod 1997; 57:312-319). In the present study, BALB/cA females mated with the males of other strains--CBA/J, C3H/HeN, C57BL/6Cr, and IXBL--showed higher pregnancy rates (66.6-87. 5%) even when they were exposed to DDK males. In the pharmacological induction of pregnancy block with dopamine agonist (bromocriptine, 4 mg/kg BW), BALB/cA females mated with BALB/cA males showed a 100% pregnancy block. In contrast, BALB/cA females mated with CBA/J, C3H/HeN, and C57BL/6Cr males showed higher pregnancy rates (40-70%). These results suggest that the better pregnancy rate of BALB/cA females mated with alien males may be due to the stronger viability of F(1) embryos. This interpretation was confirmed by an embryo transfer experiment in which a higher implantation rate was observed when BALB/cA embryos grown in BALB/cA females exposed to BALB/cA males were transferred into recipient BALB/cA females exposed to DDK males. These results suggest that the embryonic genotype or viability of the embryo is one factor contributing to the occurrence of pregnancy block by male pheromones in mice.     

Susceptibility of five strains of mice to Babesia microti of human origin.

One outbred (CF1) and four inbred (BALB/c, C57, CBA and C3H) strains of mice were tested for susceptibility to Babesia microti of human origin. Of these, intact C3H mice developed higher parasitemia than all other intact mice, while BALB/c mice developed the highest parasitemia among splenectomized mice. Susceptibility was not related to H-2 haplotype in any obvious way. Because C3H and BALB/c mice developed relatively high initial peak parasitemias, the parasite was serially passaged in both of these mouse strains in an attempt to increase parasite virulence. After 30 passages in BALB/c and 49 passages in C3H mice over a period of 12 months, maximum parasitemias were 50 times higher than those observed initially. After the peak parasitemias of these two mouse-adapted parasites had stabilized, the relationship between onset and level of maximum parasitemia and number of parasites inoculated was determined. With both C3H- and BALB/c-adapted parasites, as inoculum size increased, the time required to reach maximum parasitemia decreased and the level of maximum parasitemia increased. Studies involving infection of either mouse strain with parasites adapted to the heterologous mouse strain indicated that C3H mice were more susceptible than BALB/c mice to homologous or heterologous parasites. These data suggest that the virulence of B. microti to the mouse can be increased by prolonged passage in this host. Once adaptation to this host species has occurred, virulence appears to be more dependent on the innate susceptibility of the mouse strain than on adaptation of the parasites to a particular strain of mouse.     

Differential intra-epithelial lymphocyte phenotypes following Cryptosporidium parvum challenge in susceptible and resistant athymic strains of mice

The lack of immunocompetent laboratory animal models has limited our understanding of functional immune responses to Cryptosporidium parvum infection, but such responses have been studied in susceptible laboratory rodents with genetic, acquired, or induced immunodeficiencies. We previously observed that athymic C57BL/6J nude mice inoculated with C. parvum oocysts had lower or absent fecal oocyst excretion when compared to inoculated athymic BALB/cJ nude mice. This discrepancy prompted us to explore potential differences in intestinal immune responses in both strains. Prior to and after C. parvum challenge, BALB/cJ nude and C57BL/6J nude mice did not differ in either spleen cell numbers or in parasite-specific proliferation. However, both strains of mice exhibited a significant increase in intra-epithelial lymphocyte (IEL) numbers prior to and following C. parvum inoculation when compared to uninoculated controls (P<0.05). Prior to challenge, C57BL/6J nude mice had a higher percentage of both CD8+ and CD8+ gammadelta+ IEL than BALB/cJ nude mice. Following challenge, resistant C57BL/6J nude mice had a higher percentage of gammadelta+, CD4+, and CD8+ gammadelta+ IEL than uninoculated C57BL/6J nude mice and than susceptible BALB/cJ nude mice (P<0.05). Conversely, inoculated C57BL/6J nude mice had a significantly lower percentage of alphabeta+ IEL than inoculated BALB/cJ nude mice (P<0.05). We conclude that gammadelta+, CD4+, and/or CD8+ gammadelta+ IEL may influence responses to cryptosporidiosis in athymic murine models, and that the increased percentage of alphabeta+ IEL in susceptible BALB/cJ nude mice could reflect a preferential expression during chronic C. parvum infection and/or might downregulate local protective responses.