title: CD44high memory CD8 T cells synergize with CpG DNA to activate dendritic cell IL-12p70 production.
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 CD44(high) 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 CD8alpha(+) DCs and plasmacytoid DCs, and mediated by CD8 T cell-derived cytokines IFN-gamma, GM-CSF, TNF-alpha, and surface CD40L. We also find that CD44(high) memory phenotype CD8 T cells were better DC IL-12p70 stimulators than CD44(low) naive phenotype CD8 T cells, and this was attributed to higher levels of IFN-gamma and GM-CSF produced by CD44(high) 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.
authors.affiliation: Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore.
authors.forename: Kok Loon
authors.initials: KL
authors.lastname: Wong
authors.forename: Li Fang Melissa
authors.initials: LF
authors.lastname: Tang
authors.forename: Fei Chuin
authors.initials: FC
authors.lastname: Lew
authors.forename: Hok Sum Kenneth
authors.initials: HS
authors.lastname: Wong
authors.forename: Yen Leong
authors.initials: YL
authors.lastname: Chua
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacAry
authors.forename: David M
authors.initials: DM
authors.lastname: Kemeny
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D007156:Immunologic Memory; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000096:biosynthesis*; D053765:Interleukin-12 Subunit p35 / Q000096:biosynthesis*; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; C508859:Il12a protein, mouse; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D018664:Interleukin-12