Because of the differential expression of IL-2 in the DLN vs lung after influenza infection, we suggest that initial signals through IL-2R and possibly IL-12R delivered upon antigen recognition in the DLN are necessary to program early CD4 CTL differentiation while inflammatory signals in the lung such as IL-6 (Workman, et al in preparation) and type I IFNs [27] enhance perforin expression and killing. This evidence concerns the gene IL6 and influenza.