Yajima Toshiki, Nishimura Hitoshi, Sad Subash, Shen Hao, Kuwano Hiroyuki, Yoshikai Yasunobu
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
J Immunol. 2005 Mar 15;174(6):3590-7. doi: 10.4049/jimmunol.174.6.3590.
A rapid induction of effector functions in memory T cells provides rapid and intensified protection against reinfection. To determine potential roles of IL-15 in early expansion and activation of memory CD8+ T cells in secondary immune response, we examined the cell division and cytotoxicity of memory CD8+ T cells expressing OVA(257-264)/Kb-specific TCR that were transferred into IL-15-transgenic (Tg) mice, IL-15 knockout (KO) mice, or control C57BL/6 mice followed by challenge with recombinant Listeria monocytogenes expressing OVA (rLM-OVA). In vivo CTL activities and expression of granzyme B of the transferred CD8+ T cells were significantly higher in the IL-15 Tg mice but lower in the IL-15 KO mice than those in control mice at the early stage after challenge with rLM-OVA. In contrast, there was no difference in the cell division in IL-15 Tg mice and IL-15 KO mice compared with those in control mice. In vivo administration of rIL-15 conferred robust protection against reinfection via induction of granzyme B in the memory CD8+ T cells. These results suggest that IL-15 plays an important role in early activation of memory CD8+ T cells.
记忆T细胞效应功能的快速诱导可为再次感染提供快速且强化的保护。为了确定白细胞介素-15(IL-15)在二次免疫应答中记忆性CD8⁺T细胞早期扩增和激活中的潜在作用,我们检测了表达OVA(257 - 264)/Kb特异性TCR的记忆性CD8⁺T细胞的细胞分裂和细胞毒性,这些细胞被转入IL-15转基因(Tg)小鼠、IL-15基因敲除(KO)小鼠或对照C57BL/6小鼠,随后用表达OVA的重组单核细胞增生李斯特菌(rLM-OVA)进行攻击。在用rLM-OVA攻击后的早期阶段,IL-15 Tg小鼠中转移的CD8⁺T细胞的体内细胞毒性T淋巴细胞(CTL)活性和颗粒酶B的表达显著高于对照小鼠,而在IL-15 KO小鼠中则低于对照小鼠。相比之下,与对照小鼠相比,IL-15 Tg小鼠和IL-15 KO小鼠中的细胞分裂没有差异。体内给予重组IL-15通过诱导记忆性CD8⁺T细胞中的颗粒酶B,对再次感染提供了强大的保护。这些结果表明,IL-15在记忆性CD8⁺T细胞的早期激活中起重要作用。