CD44high memory CD8 T cells synergize with CpG DNA to activate dendritic cell IL-12p70 production.
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.
Wong
Kok Loon
KL
Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore.
Tang
Li Fang Melissa
LF
Lew
Fei Chuin
FC
Wong
Hok Sum Kenneth
HS
Chua
Yen Leong
YL
MacAry
Paul A
PA
Kemeny
David M
DM
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
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