Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Critical role of IL-15/IL-15R system for functions of antigen presenting cells

T Ohteki PhD, S Koyasu PhD

Keio University School of Medicine, Tokyo, Japan,

AIM: We have recently found that macrophages and dendritic cells (DCs) are potent in producing IFNgamma in an IL-12-dependent fashion. The amount of IFNgamma produced by the antigen presenting cells (APCs) are much higher than those from NK cells. Once IL-12 and IFNgamma are produced by DCs, a positive feedback pathway(s) would be activated between DCs and macrophages even in the absence of NK cell-derived IFNgamma. Such pathway seems important especially for an early stage of innate immune response. We further reported that IL-12-induced IFNgamma production is diminished in splenocytes isolated from common gamma chain deficient (gamma c-/- ) mice. As IL-15 type-1 receptors consisting of IL-15Ralpha, IL-2/15Rbeta and gamma c are expressed on APCs, we examined the role of IL-15/IL-15R system in their development and/or functional maturation. METHODS: DCs and macrophages were freshly isolated from spleens of gamma c-/-, IL-2/15Rbeta-/-, IL-15-/-, and IL-2-/- mice. These cells were cultured in the presence of IL-12, IL-18, LPS, and Listeria monocytogenes for 3 days. Amounts of IFNgamma and NO produced by DCs and/or macrophages were determined by ELISA and Greiss reagent, respectively. RESULTS: DCs and macrophages are present in gamma c-/- and IL-2/15Rbeta-/- mice, but they are severely impaired in production of IFNgamma and NO. Similar phenotypes were observed in DCs and macrophages of IL-15-/- mice but not in those of IL-2-/- mice. CONCLUSIONS: These results demonstrate that IL-15/IL-15R interaction is critical in early activation of APCs and plays an important role in the innate immune system.

KEY WORDS: dendritic cells, macrophages, IFNgamma, nitric oxide, .

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunotherapy.