Submitted October 23, 2006
Accepted February 26, 2007
TLR3 ligand stimulates fully functional memory CD8+ T-cells in the absence of CD4+ T-cell help
Sandra Hervas-Stubbs, Aurelie Olivier, Florence Boisgerault, Nathalie Thieblemont, and Claude Leclerc*
Unite de Regulation Immunitaire et Vaccinologie, Institut Pasteur, Paris, France
INSERM U833, Paris, France
Centre National de la Recherche Scientifique (CNRS-UMR 8147), University Rene Descartes Paris V, Hopital Necker, Paris, France
* Corresponding author; email: cleclerc{at}pasteur.fr.
We investigated whether Toll-like receptors ligands (TLR-Ls) can bypass the requirement for CD4+ T-cell help in the induction of fully efficient memory CD8+ T-cells (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 upregulation 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-
/
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.
