Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice.

Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice.
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DOI:
10.1084/jem.191.5.771
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发表时间:
2000-03-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Peschon JJ
Peschon JJ
中科院分区:
其他
文献类型:
--
作者:
Kennedy MK;Glaccum M;Brown SN;Butz EA;Viney JL;Embers M;Matsuki N;Charrier K;Sedger L;Willis CR;Brasel K;Morrissey PJ;Stocking K;Schuh JC;Joyce S;Peschon JJ

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通过基因靶向产生白细胞介素15遗传缺陷的C57 BL/6小鼠(IL-15−/−小鼠)。IL-15−/−小鼠的胸腺和外周自然杀伤(NK)T细胞、记忆表型CD 8 + T细胞和肠上皮内淋巴细胞(IEL)的不同亚群数量显著减少。IL-15−/−小鼠中这些细胞群的减少但并非不存在,可能反映了IL-15在这些细胞的扩增和/或存活中的重要作用。通过免疫表型和功能标准评估,IL-15−/−小鼠缺乏NK细胞,表明IL-15在NK细胞的发育和功能成熟中具有专性作用。与IL-15缺乏相关的特定缺陷通过体内施用外源性IL-15来逆转。尽管IL-15−/−小鼠存在免疫缺陷,但在无特定病原体的条件下保持健康。然而,IL-15−/−小鼠可能对各种病原体的宿主防御反应受损,因为它们无法对牛痘病毒的攻击产生保护性反应。这些数据揭示了IL-15在特定淋巴谱系发育中的关键作用。此外,通过IL-15给药挽救IL-15−/−小鼠淋巴缺陷的能力代表了进一步阐明这种细胞因子的生物学作用的有力手段。
C57BL/6 mice genetically deficient in interleukin 15 (IL-15−/− mice) were generated by gene targeting. IL-15−/− mice displayed marked reductions in numbers of thymic and peripheral natural killer (NK) T cells, memory phenotype CD8+ T cells, and distinct subpopulations of intestinal intraepithelial lymphocytes (IELs). The reduction but not absence of these populations in IL-15−/− mice likely reflects an important role for IL-15 for expansion and/or survival of these cells. IL-15−/− mice lacked NK cells, as assessed by both immunophenotyping and functional criteria, indicating an obligate role for IL-15 in the development and functional maturation of NK cells. Specific defects associated with IL-15 deficiency were reversed by in vivo administration of exogenous IL-15. Despite their immunological defects, IL-15−/− mice remained healthy when maintained under specific pathogen-free conditions. However, IL-15−/− mice are likely to have compromised host defense responses to various pathogens, as they were unable to mount a protective response to challenge with vaccinia virus. These data reveal critical roles for IL-15 in the development of specific lymphoid lineages. Moreover, the ability to rescue lymphoid defects in IL-15−/− mice by IL-15 administration represents a powerful means by which to further elucidate the biological roles of this cytokine.
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