Submitted May 13, 2008
Accepted September 2, 2008
Dendritic cells drive memory CD8 T cell homeostasis via IL-15 trans-presentation
Spencer W Stonier, Lisa J Ma, Eliseo F Castillo, and Kimberly S Schluns*
Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
* Corresponding author; email: kschluns{at}mdanderson.org.
Interleukin (IL)-15 is crucial for the development of naive and memory CD8 T cells and delivered through a mechanism call trans-presentation. Previous studies showed that memory CD8 T cells require IL-15 trans-presentation by an as of yet unknown cell of hematopoietic origin. We hypothesized that dendritic cells (DC) trans-present IL-15 to CD8 T cells and examined this by developing a transgenic model that limits IL-15 trans-presentation to DCs. In this study, IL-15 trans-presentation by DCs had little effect on restoring naive CD8 T cells but contributed to the development of memory-phenotype CD8 T cells. The generation of virus-specific, memory CD8 T cells was partially supported by IL-15R
+ DCs through the preferential enhancement of a subset of KLRG-1+CD27- CD8 T cells. In contrast, these DCs were largely sufficient in driving normal homeostatic proliferation of established memory CD8 T cells suggesting that memory CD8 T cells grow more dependent on IL-15 trans-presentation by DCs. Overall, our study clearly supports a role for DCs in memory CD8 T cell homeostasis but also provides evidence that other hematopoietic cells are involved in this function. The identification of DCs fulfilling this role will enable future studies to better focus on mechanisms regulating T cell homeostasis.
