Studies with MHC-deficient knock-out mice reveal impact of both MHC I- and MHC II-dependent T cell responses on Listeria monocytogenes infection.
Studies with MHC-deficient knock-out mice reveal impact of both MHC I- and MHC II-dependent T cell responses on Listeria monocytogenes infection.
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对 MHC 缺陷型敲除小鼠的研究揭示了 MHC I 和 MHC II 依赖性 T 细胞反应对单核细胞增生李斯特菌感染的影响。
DOI：
10.4049/jimmunol.154.8.4223.d
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发表时间：
1994
影响因子：
4.4
通讯作者：
S. Kaufmann
中科院分区：
文献类型：
--
作者：
C. Ladel;I. Flesch;J. Arnoldi;S. Kaufmann
使用在β 2-微球蛋白（β 2 m）或H2-I-A β链中具有确定的遗传缺陷的突变小鼠（它们分别几乎缺乏功能性CD 8或CD 4 α β T细胞）来分析涉及对单核细胞增多性李斯特菌获得性抗性的免疫机制。虽然L.与它们的杂合对照同窝出生的小鼠相比，任一小鼠突变体的单核细胞增多症显著降低，β m -/-和A β-/-突变体都能够解决低剂量感染。然而，在这两种突变小鼠中，病程加重，清除明显延迟。疫苗诱导的免疫力对第二次高剂量感染的幼稚动物致死也受损β 2 m-/-和A β-/-小鼠。然而，这两种突变小鼠仍然能够控制继发感染。根据L.在脾脏单核细胞增生性微生物中，β 2 m-/-突变体比A β-/-小鼠遭受更显著的原发和继发感染。Ag诱导的IFN-γ分泌在β 2 m-/-小鼠感染的早期阶段和A β-/-小鼠感染的后期阶段受损。通过mAb处理对γ δ T细胞的调节导致β 2 m-/-和A β-/-小鼠脾脏细菌负荷的显著增加。最后，两种突变体的肉芽肿病变的发展都受到显着影响。在β 2 m-/-突变体中，出现浸润性病变，在A β-/-小鼠中，几乎没有出现具有坏死中心的炎性胰岛。这些数据证明了MHC I和MHC II依赖性免疫机制在获得性抗L。单核细胞增生和点之间的协调相互作用的必要性CD 8和CD 4 α β T细胞（和可能γ δ T细胞）在抗L。单核细胞增多症抗性。
Mutant mice with a defined genetic defect in the beta 2-microglobulin (beta 2m) or the H2-I-A beta chain, which are virtually devoid of functional CD8 or CD4 alpha beta T cells, respectively, were employed for analyzing immune mechanisms involved in acquired resistance against Listeria monocytogenes. Although the lethal dose of L. monocytogenes was markedly lower for either mouse mutant as compared with their heterozygous control littermates, both beta m -/- and A beta -/- mutants were able to resolve low dose infection. However, in both mouse mutants, the course of disease was exacerbated and clearance was markedly delayed. Vaccine induced immunity against a secondary high dose infection lethal for naive animals was also impaired in beta 2m -/- and A beta -/- mice. However, both mutant mice were still capable of controlling secondary infection. Based on numbers of L. monocytogenes organisms in spleens, beta 2m -/- mutants suffered more dramatically from primary and secondary infection than A beta -/- mice. Ag-induced IFN-gamma secretion was impaired during the early phase of infection in beta 2m -/- mice and at later stages in A beta -/- mice. Modulation of gamma delta T cells by mAb treatment led to significant increase in bacterial load of spleens in both beta 2m -/- and A beta -/- mice. Finally, the development of granulomatous lesions was markedly affected in both mutants. In beta 2m -/- mutants, infiltrative lesions appeared and in A beta -/- mice few inflammatory islets with necrotic centers developed. These data demonstrate the importance of both MHC I- and MHC II-dependent immune mechanisms in acquired resistance to L. monocytogenes and point to the necessity of a coordinated interaction between CD8 and CD4 alpha beta T cells (and probably gamma delta T cells) in anti-L. monocytogenes resistance.