Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation.
Interleukin-15 (IL-15) is crucial for the development of naive and memory CD8 T cells and is delivered through a mechanism called transpresentation. Previous studies showed that memory CD8 T cells require IL-15 transpresentation by an as yet unknown cell of hematopoietic origin. We hypothesized that dendritic cells (DCs) transpresent IL-15 to CD8 T cells, and we examined this by developing a transgenic model that limits IL-15 transpresentation to DCs. In this study, IL-15 transpresentation 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-15Ralpha(+) 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 transpresentation 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.
Stonier
Spencer W
SW
Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ma
Lisa J
LJ
Castillo
Eliseo F
EF
Schluns
Kimberly S
KS
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D039521:CD11c Antigen / Q000235:genetics / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics / Q000502:physiology*; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D053720:Interleukin-15 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic
D039521:CD11c Antigen; D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit