Distinct requirements for the cytokine-mediated activation of NKT and NK cells during viral infection. (45.16)

Abstract

Abstract Innate immune cells respond rapidly and provide protection early following infections. We have studied the roles of two innate lymphocyte cell types, natural killer (NK) cells and natural killer T cells (NKT cells) in the protective response to mouse cytomegalovirus (MCMV), a β herpes virus infection. The importance of NK cells for host protection following this infection had been known for many years, but here we establish that NKT cells are also important and that the two cell types have different cytokine requirements for optimal induction of IFNγ. NKT cells are most sensitive to IL-12, when a small amount of IL-18 is present. NK cells, by contrast, are more responsive to IFNβ combined with either IL-18 or IL-12. We further demonstrate that the two cell types are not redundant by identifying dendritic cells, that when infected with MCMV, activates NK cells but does not necessarily activate NKT cells. Consistent with these findings, the activation of NKT cells following MCMV infection was more drastically decreased; compared to NK cells, in mice lacking the ability to produce IL-12. BALB/c mice deficient for NKT cells had increased viral titers, and depletion of NK cells led to a further increase. Our data indicate that NKT and NK cells are both required for maximal MCMV protection, and that they have different requirements for cytokine mediated activation and may reflect the activity of different types of infected antigen presenting cells.