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IL‐15‐induced CD8 + CD122 + T cells increase antibacterial and anti‐tumor immune responses: implications for immune function in aged mice
Author(s) -
Motegi Akira,
Kinoshita Manabu,
Inatsu Akihito,
Habu Yoshiko,
Saitoh Daizoh,
Seki Shuhji
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0807530
Subject(s) - biology , cd8 , immune system , spleen , cytotoxic t cell , immunology , perforin , in vitro , biochemistry
We previously proposed that mouse CD8 + CD122 + T cells and human CD57 + T cells, which increase with age and exhibit potent IFN‐γ 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‐γ 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‐γ) 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.