Yajima T, Nishimura H, Ishimitsu R, Yamamura K, Watase T, Busch D H, Pamer E G, Kuwano H, Yoshikai Y
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya, Japan.
Eur J Immunol. 2001 Mar;31(3):757-66. doi: 10.1002/1521-4141(200103)31:3<757::aid-immu757>3.0.co;2-q.
We recently constructed IL-15 transgenic (Tg) mice using cDNA encoding a secretable isoform of the IL-15 precursor protein under the control of an MHC class I promoter. The IL-15 Tg mice exhibited resistance against a primary infection with Listeria monocytogenes. The numbers of memory CD8(+) T cells were markedly increased in the IL-15 Tg mice following Listeria infection accompanied by sustained IL-15 production. The increased CD44(+)CD8(+) T cells in the infected IL-15 Tg mice were not specialized to recognize Listeria-specific antigen but produced a large amount of IFN-gamma in response to bystander stimulation exogenous IL-15 in combination with IL-12. Furthermore, Listeria-specific Th1 response by CD4(+) T cells was significantly augmented in the IL-15 Tg mice compared with control mice following Listeria infection. In vivo depletion of the CD8(+) T cells by anti-CD8 monoclonal antibody and adoptive transfer of the T cells from naive IL-15 Tg mice indicated that the CD8(+) T cells functioned not only to eliminate bacteria at the early stage of infection but also to promote Th1 response to L. monocytogenes. Overexpression of IL-15 shed light on a novel role of memory CD8(+) T cells in early protection and promotion of Th1 response against a primary infection with L. monocytogenes.
我们最近构建了IL-15转基因（Tg）小鼠，其使用在MHC I类启动子控制下编码IL-15前体蛋白的可分泌异构体的cDNA。IL-15 Tg小鼠对单核细胞增生李斯特菌的原发性感染表现出抗性。在单核细胞增生李斯特菌感染后，IL-15 Tg小鼠中记忆性CD8(+) T细胞的数量显著增加，并伴有持续的IL-15产生。感染的IL-15 Tg小鼠中增加的CD44(+)CD8(+) T细胞并非专门识别李斯特菌特异性抗原，而是在受到旁观者刺激时，对外源IL-15与IL-12的组合产生大量的IFN-γ。此外，与对照小鼠相比，在单核细胞增生李斯特菌感染后，IL-15 Tg小鼠中CD4(+) T细胞介导的李斯特菌特异性Th1反应显著增强。用抗CD8单克隆抗体在体内清除CD8(+) T细胞，并从幼稚的IL-15 Tg小鼠中过继转移T细胞，结果表明CD8(+) T细胞不仅在感染早期发挥清除细菌的作用，还能促进对单核细胞增生李斯特菌的Th1反应。IL-15的过表达揭示了记忆性CD8(+) T细胞在针对单核细胞增生李斯特菌原发性感染的早期保护和促进Th1反应中的新作用。
