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A Novel Role of IL-15 in Early Activation of Memory CD8⁺ CTL after Reinfection¹

Toshiki Yajima^2,*,, Hitoshi Nishimura^*, Subash Sad, Hao Shen, Hiroyuki Kuwano and Yasunobu Yoshikai^*

^* Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; First Department of Surgery, Gunma University School of Medicine, Maebashi, Japan; Laboratory of Cellular Immunology, Institute for Biological Sciences, National Research Council of Canada, Ontario, Canada; and Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104

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/K^b-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.

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