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

Abstract

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.

• Authors: Akira Motegi, Manabu Kinoshita, Akihito Inatsu, Yoshiko Habu, Daizoh Saitoh, Shuhji Seki
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 84 Issue 4 Pg. 1047-56 (Oct 2008) ISSN: 0741-5400 [Print] United States
• PMID: 18653461 (Publication Type: Journal Article)

Chemical References

• CD8 Antigens
• Interleukin-15
• Interleukin-2 Receptor beta Subunit
• Interferon-gamma

Topics

• Aging (immunology)
• Animals
• Bacterial Infections (immunology)
• CD8 Antigens (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Escherichia coli Infections (immunology, mortality)
• Flow Cytometry
• Interferon-gamma (immunology)
• Interleukin-15 (therapeutic use)
• Interleukin-2 Receptor beta Subunit (immunology)
• Killer Cells, Natural (immunology)
• Liver Neoplasms, Experimental (immunology)
• Lymphocyte Depletion
• Mice
• Mice, Inbred C57BL
• Neoplasms, Experimental (immunology)
• Survival Analysis
• Survivors