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Kok Loon Wong, Li Fang Melissa Tang, Fei Chuin Lew, Hok Sum Kenneth Wong, Yen Leong Chua, Paul A MacAry, David M Kemeny, CD44high Memory CD8 T Cells Synergize with CpG DNA to Activate Dendritic Cell IL-12p70 Production, The Journal of Immunology, Volume 183, Issue 1, July 2009, Pages 41–50, https://doi.org/10.4049/jimmunol.0803473
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Abstract
Protective memory CD8 T cell responses are generally associated with the rapid and efficient acquisition of CTL function. However, the ability of memory CD8 T cells to modulate immune responses through interactions with dendritic cells (DCs) during the early states of secondary Ag exposure is poorly understood. In this study, we show that murine Ag-specific CD44high CD8 T cells, representing CD8 T cells of the memory phenotype, potently activate DCs to produce high levels of IL-12p70 in conjunction with stimulation of DCs with the TLR 9 ligand, unmethylated CpG DNA. IL-12p70 production was produced predominantly by CD8α+ DCs and plasmacytoid DCs, and mediated by CD8 T cell-derived cytokines IFN-γ, GM-CSF, TNF-α, and surface CD40L. We also find that CD44high memory phenotype CD8 T cells were better DC IL-12p70 stimulators than CD44low naive phenotype CD8 T cells, and this was attributed to higher levels of IFN-γ and GM-CSF produced by CD44high memory phenotype CD8 T cells during their Ag specific interaction with DCs. Our study identifies CpG DNA as the most effective TLR ligand that cooperates with CD8 T cells for DC IL-12p70 production, and suggests that effectiveness of memory CD8 T cells could be attributed to their ability to rapidly and effectively induce protective Th1 immunity during early stages of pathogen reinfection.
