TNFR-TNFL superfamily member interactions induced by combined TLR/CD40 stimulation act as Signal 3 for enhanced CD8+ T cell immunity (44.10)

Abstract Previously, we have shown that antigen-specific CD8+ T cell expansion following TLR agonist/anti-CD40 immunization is dependent on the enhanced expression of CD70 on dendritic cells. The dependence on CD27-CD70 interactions was confirmed by using a blocking anti-CD70 antibody. We now show that in CD27-/- mice, the antigen-specific CD8+ T cell response to TLR agonist/anti-CD40 immunization is intact. However, administration of a blocking anti-OX40L antibody during immunization attenuates the CD8+ T cell expansion. Thus, similar to the wild-type C57BL/6 mice, the enhanced primary expansion of antigen-specific CD8+ T cells in response to TLR agonist/anti-CD40 vaccination is dependent on TNF receptor (TNFR) - TNF ligand (TNFL) superfamily interactions. Furthermore, TLR agonist/anti-CD40 vaccination is not affected by depletion of IL-12 using a neutralizing anti-IL-12p40 antibody in either wild-type or CD27-/- mice. Together, these data suggest that TNFR-TFNL interactions, facilitated by combined TLR agonist/anti-CD40 vaccination, can act as Signal 3 for CD8+ T cell immunity in the absence of IL-12. This research is supported by a grant from the NIH.