TLR3 ligand stimulates fully functional memory CD8+ T cells in the absence of CD4+ T-cell help.
We investigated whether Toll-like receptor ligands (TLR-Ls) can bypass the requirement for CD4(+) T-cell help in the induction of fully efficient memory CD8(+) T cells (cytotoxic T lymphocytes [CTLs]). "Helpless" CTLs were induced by a synthetic CD8(+) T-cell epitope administered with TLR3-L and TLR9-L, but not with TLR2/6-L, TLR4-L, or TLR7-L. The up-regulation of MHC-I and costimulatory molecules by dendritic cells following TLR stimulation was not sufficient for the priming of "helpless" CTLs, which depended essentially on the induction of a strong IFN-alpha/beta response. The "helpless" CTLs induced by TLR-Ls differentiated into fully functional memory CTLs able to proliferate as well as their "helped" counterparts upon challenge, in the absence of CD4(+) T-cell help.
Hervas-Stubbs
Sandra
S
Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France.
Olivier
Aurélie
A
Boisgerault
Florence
F
Thieblemont
Nathalie
N
Leclerc
Claude
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D049109:Cell Proliferation; D045142:Cross-Priming; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000494:pharmacology; D007156:Immunologic Memory; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
D018984:Epitopes, T-Lymphocyte; D008024:Ligands; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3