Requirement for CD70 in CD4+ Th cell-dependent and innate receptor-mediated CD8+ T cell priming

Dendritic cell (DC) conditioning by CD4(+) T cells, or via engagement of innate receptors, is thought to be essential for CD8(+) T cell priming. However, the molecular features that distinguish a conditioned DC from an unconditioned DC are poorly defined. In this study. we investigate the role of CD70, a member of the TNF superfamily that is expressed on activated DC, in CD4+ Th-dependent and -independent CD8(+) T cell responses. We demonstrate that CD70 is required for CD4(+) T cell-dependent priming of CD8(+) T cells as well as priming mediated by the viral signature, dsRNA. Accordingly, mice that were subjected to CD70 blockade during the primary response fail to generate a memory CD8(+) T cell response. Furthermore, we find that CD70 is dispensable for CD4(+) T cell expansion and help for B cells, thus suggesting a direct role for CD70 in CD8(+) T cell priming. Our results show that the innate and adaptive (CD4(+) T cells) arms of the immune system use a common signaling pathway in driving CD8(+) T cell responses and suggest that expression of CD70 on DC represents the hallmark of conditioned DC.