Chronic active hepatitis induced by Helicobacter hepaticus in the A/JCr mouse is associated with a Th1 cell-mediated immune response

Chronic active hepatitis induced by Helicobacter hepaticus in the A/JCr mouse is associated with a Th1 cell-mediated immune response
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DOI:
10.1128/iai.66.7.3142-3148.1998
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发表时间:
1998-07-01
影响因子:
3.1
通讯作者:
Fox, JG
Fox, JG
中科院分区:
医学2区
文献类型:
--
作者:
Whary, MT;Morgan, TJ;Fox, JG

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A/JCr小鼠的肝螺杆菌感染导致慢性活动性肝炎,其特征为血管周围、门静脉周围和实质单核细胞和多形核细胞浸润。本研究观察了A/JCr小鼠对H.肝感染通过测量感染后(p.i.)血清、粪便和胆汁中的抗体应答以及脾单核细胞对H.肝抗原免疫后4周产生分泌性免疫球蛋白A(伊加)和全身性IgG 2a抗体。并持续了12个月。感染小鼠的脾细胞增殖,并产生更多的γ干扰素(IFN-γ)比白细胞介素-IL(IL-4)或IL-5时,AT。肝外膜蛋白血清中主要的IgG 2a抗体应答和体外产生的IFN-γ超过IL-4或IL-5是一致的,分别与感染幽门螺杆菌和猫螺杆菌的人和小鼠中报道的Th 1免疫应答一致。感染H.肝细胞逐渐发展为严重的血管周围、门静脉周围和肝实质病变,包括淋巴组织细胞和浆细胞浸润。此外,在感染后12个月观察到透壁性盲肠炎。细胞介导的针对H.在A/JCr小鼠中的肝感染应该证明作为操纵宿主对螺杆菌的反应的实验方案的模型是有价值的。
Helicobacter hepaticus infection in A/JCr mice results in chronic active hepatitis characterized by perivascular, periportal, and parenchymal infiltrates of mononuclear and polymorphonuclear cells. This study examined the development of hepatitis and the immune response of A/JCr mice to H. hepaticus infection. The humoral and cell-mediated T helper immune response was profiled by measuring the postinfection (p.i.) antibody response in serum, feces, and bile and by the production of cytokines and proliferative responses by splenic mononuclear cells to H. hepaticus antigens. Secretory immunoglobulin A (IgA) and systemic IgG2a antibody developed by 4 weeks p.i. and persisted through 12 months. Splenocytes from infected mice proliferated and produced more gamma interferon (IFN-gamma) than interleukin-il (IL-4) or IL-5 when cultured with AT. hepaticus outer membrane proteins. The predominantly IgG2a antibody response in serum and the in vitro production of IFN-gamma in excess of IL-4 or IL-5 are consistent,with a Th1 immune response reported in humans and mice infected with Helicobacter pylori and Helicobacter felis, respectively. Mice infected with H. hepaticus developed progressively severe perivascular, periportal, and hepatic parenchymal lesions consisting of lymphohistiocytic and plasmacytic cellular infiltrates. In addition, transmural typhlitis was observed at 12 months p.i. The characterization of a cell-mediated Th1 immune response to H. hepaticus infection in the A/JCr mouse should prove valuable as a model for experimental regimens which manipulate the host response to Helicobacter.