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Published online before print July 23, 2008

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(Journal of Leukocyte Biology. 2008;84:1047-1056.)
© 2008 by Society for Leukocyte Biology

IL-15-induced CD8⁺CD122⁺ T cells increase antibacterial and anti-tumor immune responses: implications for immune function in aged mice

Akira Motegi^*, Manabu Kinoshita^*, Akihito Inatsu, Yoshiko Habu^*, Daizoh Saitoh and Shuhji Seki^*,1

^* Department of Immunology and Microbiology, National Defense Medical College,
Division of Traumatology, National Defense Medical College Research Institute, and
Department of Laboratory Medicine, National Defense Medical College Hospital, Tokorozawa, Japan

¹ Correspondence: Department of Microbiology, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan. E-mail: btraums{at}ndmc.ac.jp

We previously proposed that mouse CD8⁺CD122⁺ T cells and human CD57⁺ T cells, which increase with age and exhibit potent IFN- production, represent a double-edged sword as they play critical roles in host defense and the lethal IL-12/LPS-induced generalized Shwartzman reaction (GSR). However, our proposal was based solely on comparisons of young and old mice. In this study, we attempted to increase CD8⁺CD122⁺ T cells in young mice with exogenous IL-15 and confirm their countervailing functions in young mice. After young mice (6 weeks) were injected with IL-15, they showed significant increases in CD8⁺CD122⁺ T cells in the liver and spleen. Liver CD8⁺CD122⁺ T cells from IL-15-pretreated mice had a potent capacity to produce IFN- after IL-12 injection or Escherichia coli infection. IL-15-pretreated mice showed increased survival to E. coli infections and enhanced anti-tumor activities against liver metastatic EL4 cells, as well as an exacerbation of the GSR. Correspondingly, liver CD8⁺CD122⁺ T cells produced more perforin than CD8⁺CD122^– T cells in EL4-inoculated mice. Unexpectedly, comparable IL-15 treatment did not induce further increases in CD8⁺CD122⁺ T cells in aged mice and did not enhance their defenses against bacterial infection or tumor growth. Interestingly, however, nontreated, aged mice (50 weeks) showed twofold higher IL-15 levels (but not TNF or IFN-) in liver homogenates compared with young mice. Our results further support that CD8⁺CD122⁺ T cells, which are increased physiologically or therapeutically by IL-15, are involved in antibacterial immunity, anti-tumor immunity, and the GSR.

Key Words: generalized Shwartzman reaction • infection • cytotoxicity • EL4 • liver immunity • innate immunity