IL-15-induced CD8+CD122+ T cells increase antibacterial and anti-tumor immune responses: implications for immune function in aged mice.
We previously proposed that mouse CD8(+)CD122(+) T cells and human CD57(+) T cells, which increase with age and exhibit potent IFN-gamma 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-gamma 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-gamma) 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.
Motegi
Akira
A
Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa 359-8513, Japan.
Kinoshita
Manabu
M
Inatsu
Akihito
A
Habu
Yoshiko
Y
Saitoh
Daizoh
D
Seki
Shuhji
S
D000818:Animals; D051379:Mice; D000375:Aging / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology / Q000401:mortality; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology; D019409:Interleukin-15 / Q000627:therapeutic use; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000276:immunology; D008212:Lymphocyte Depletion; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology; D016019:Survival Analysis
D016827:CD8 Antigens; D007371:Interferon-gamma; D019409:Interleukin-15; D053646:Interleukin-2 Receptor beta Subunit