Harty J T, Bevan M J
Department of Microbiology, University of Iowa, Iowa City 52242, USA.
Immunity. 1995 Jul;3(1):109-17. doi: 10.1016/1074-7613(95)90163-9.
Cytokine and cytokine receptor gene knockout mice provide powerful experimental systems to characterize the functions of these molecules in resistance to infectious disease. Such mice may also provide unique models of immune deficiency to learn whether manipulation of the immune response can overcome the specific dysfunction. We demonstrate that resistance of IFN gamma gene knockout (GKO-/-) mice to the intracellular bacterium Listeria monocytogenes is severely impaired compared with wild-type mice. However, immunization of GKO-/- mice with an attenuated L. monocytogenes strain generates antigen-specific CD8 T cell responses that can transfer immunity to naive hosts. Furthermore, vaccinated GKO-/- mice themselves exhibit 20,000-fold increased resistance to challenge with virulent L. monocytogenes and this resistance appears to be CD8 T cell mediated. These studies demonstrate that vaccination-induced immunity can overcome the absence of a cytokine that is critical for resistance to acute infection.
细胞因子和细胞因子受体基因敲除小鼠提供了强大的实验系统，以表征这些分子在抵抗传染病中的功能。此类小鼠还可能提供独特的免疫缺陷模型，以了解免疫反应的操控是否能够克服特定的功能障碍。我们证明，与野生型小鼠相比，干扰素γ基因敲除（GKO-/-）小鼠对细胞内细菌单核细胞增生李斯特菌的抵抗力严重受损。然而，用减毒单核细胞增生李斯特菌菌株免疫GKO-/-小鼠会产生抗原特异性CD8 T细胞反应，该反应可将免疫力转移至未感染的宿主。此外，接种疫苗的GKO-/-小鼠自身对强毒单核细胞增生李斯特菌攻击的抵抗力增加了20000倍，且这种抵抗力似乎是由CD8 T细胞介导的。这些研究表明，疫苗诱导的免疫力可以克服缺乏对抵抗急性感染至关重要的细胞因子的情况。
