CD8+ T Cells Sabotage Their Own Memory Potential through IFN-γ–Dependent Modification of the IL-12/IL-15 Receptor α Axis on Dendritic Cells

CD8 + T cell responses have been shown to be regulated by dendritic cells (DCs) and CD4 + T cells, leading to the tenet that CD8 + T cells play a passive role in their own differentiation. In contrast, by using a DNA vaccination model, to separate the events of vaccination from those of CD8 + T cell priming, we demonstrate that CD8 + T cells, themselves, actively limit their own memory potential through CD8 + T cell-derived IFN-γ–dependent modification of the IL-12/IL-15Rα axis on DCs. Such CD8 + T cell-driven cytokine alterations result in increased T-bet and decreased Bcl-2 expression, and thus decreased memory progenitor formation. These results identify an unrecognized role for CD8 + T cells in the regulation of their own effector differentiation fate and a previously uncharacterized relationship between the balance of inflammation and memory formation.