Selected Toll-like receptor ligands and viruses promote helper-independent cytotoxic T cell priming by upregulating CD40L on dendritic cells.
CD40L (CD154) on CD4(+) T cells has been shown to license dendritic cells (DCs) via CD40 to prime cytotoxic T lymphocyte (CTL) responses. We found that the converse (CD40L on DCs) was also important. Anti-CD40L treatment decreased endogenous CTL responses to both ovalbumin and influenza infection even in the absence of CD4(+) T cells. DCs expressed CD40L upon stimulation with agonists to Toll-like receptor 3 (TLR3) and TLR9. Moreover, influenza infection, which stimulates CTLs without help, upregulated CD40L on DCs, but herpes simplex infection, which elicits CTLs through help, did not. CD40L-deficient (Cd40lg(-/-)) DCs are suboptimal both in vivo in bone marrow chimera experiments and in vitro in mixed lymphocyte reactions. In contrast, Cd40lg(-/-) CD8(+) T cells killed as effectively as wild-type cells. Thus, CD40L upregulation on DCs promoted optimal priming of CD8(+) T cells without CD4(+) T cells, providing a mechanism by which pathogens may elicit helper-independent CTL immunity.
Johnson
Susan
S
Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australiaia.
Zhan
Yifan
Y
Sutherland
Robyn M
RM
Mount
Adele M
AM
Bedoui
Sammy
S
Brady
Jamie L
JL
Carrington
Emma M
EM
Brown
Lorena E
LE
Belz
Gabrielle T
GT
Heath
William R
WR
Lew
Andrew M
AM
D000818:Animals; D000906:Antibodies / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D019013:CD40 Antigens; D008024:Ligands; D051193:Toll-Like Receptors; D023201:CD40 Ligand