Switching from a restricted to an effective CD4 T cell response by activating CD8+ murine dendritic cells with a Toll-like receptor 9 ligand.
Freshly isolated quiescent splenic dendritic cell (DC) subtypes differ in their capacity to activate naive CD4 T cells in culture. The CD8+ DC showed a reduced capacity to stimulate T cell proliferation compared to either of the CD8- DC subsets, regardless of antigen and DC dose. In contrast to CD8- DC, the quiescent CD8+ DC did not induce IFN-gamma production from CD4 T cells. The difference between the DC subtypes appeared to be at the level of initial surface molecule interactions, but could not be attributed to differences in expression of MHC class II or B7 family molecules, or to the expression of Fas ligand on DC. However, when activated by inclusion of the Toll-like receptor 9 ligand CpG in culture, CD8+ DC became potent stimulators of both CD4 T cell proliferation and IFN-gamma production. In contrast, similar activation of CD8- DC produced a more modest increase in capacity to stimulate CD4 T cell proliferation and no increase in capacity to stimulate IFN-gamma production. The difference between a quiescent and an activated state is therefore more extreme for CD8+ than for CD8- DC. The especially tight regulation of the activity of CD8+ DC may be essential for the maintenance of self tolerance.
Rizzitelli
Alexandra
A
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Vremec
David
D
Villadangos
Jose A
JA
Mavaddat
Nasim
N
Wright
Mark D
MD
Shortman
Ken
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D053222:Fas Ligand Protein; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000378:metabolism; D019014:fas Receptor
D016827:CD8 Antigens; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D015850:Interleukin-6; D008024:Ligands; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D016753:Interleukin-10; D007371:Interferon-gamma