Submitted March 27, 2008
Accepted March 2, 2009
Costimulatory ligand CD70 allows induction of CD8+ T cell immunity by immature dendritic cells in a vaccination setting
Anna M. Keller, Yanling Xiao, Victor Peperzak, Shalin H. Naik, and Jannie Borst*
Division of Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands
* Corresponding author; email: j.borst{at}nki.nl.
The use of dendritic cells (DCs) as anti-cancer vaccines holds promise for therapy, but requires optimization. We have explored the potential of costimulatory ligand CD70 to boost the capacity of DCs to evoke effective CD8+ T cell immunity. We demonstrate that immature conventional DCs, when endowed with CD70 expression by transgenesis, are converted from a tolerogenic state into an immunogenic state. Adoptively transferred CD70-expressing immature DCs could prime CD8+ T cells - via CD27 - to become tumor-eradicating cytolytic effectors and memory cells with a capacity for robust secondary expansion. The CD8+ T cell response, including memory programming, was independent of CD4+ T cell help, since the transferred immature DCs were loaded with MHC class I-restricted peptide only. Without CD70 expression, the DCs generated abortive clonal expansion, dysfunctional anti-tumor responses and no CD8+ T cell memory. CD70-expressing CD8+ DCs were the primary subset responsible for CD8+ T cell priming and performed comparably to fully matured DCs. These data highlight the importance of CD27/CD70 interactions at the T cell/DC interface and indicate that CD70 should be considered in the design of DC vaccination strategies.
