An alternative signal 3: CD8+ T cell memory independent of IL-12 and type I IFN is dependent on CD27/OX40 signaling

► CD8+ T cell memory can be produced independent of the signal 3 mediators type I IFN and IL-12. ► IFN/IL-12 independent T cell memory is compromised in the absence of the TNF receptors CD27 and OX40. ► CD27/OX40 are non-cytokine signal 3 mediators of CD8+ T cell immunity. ► Combined TLR/CD40 vaccination elicits IFN/IL-12 independent, CD27/OX40-dependent immunity.