Defective CD40-dependent antigen cross-priming of CD8+ T cells in mice with conditional deletion of NF-κB-inducing kinase (146.11)

Dendritic cells (DCs) link innate and adaptive immunity, using a host of innate immune and inflammatory receptors to respond to pathogens and inflammatory stimuli. While canonical NF-κB signaling within DCs is clearly important for many of these responses, the role of non-canonical NF-κB signaling via the serine/threonine kinase NIK needs clarification. To investigate the function of NIK in DC stimulus responses and immunity, we generated transgenic mice with targeted NIK deletion in CD11c+ DCs. We observe that conditional deletion of NIK impairs CD40-dependent cross-priming of naive CD8 T cells in vivo and deficient CD40-stimulated antigen cross-presentation and IL-12p40 secretion by splenic-derived DCs in vitro. In human monocyte-derived DCs after siRNA silencing of NIK in vitro, we observe a similar IL-12p40 secretion defect. These findings suggest that NIK serves to transmit a ‘DC licensing’ signal from CD4 T helper cells to naive CD8 T cells during antigen cross-priming of a CD8 T cell response.