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 Blood, 15 June 2007, Vol. 109, No. 12, pp. 5318-5326.
Prepublished online as a Blood First Edition Paper on March 5, 2007; DOI 10.1182/blood-2006-10-053256.

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IMMUNOBIOLOGY

TLR3 ligand stimulates fully functional memory CD8+ T cells in the absence of CD4+ T-cell help

Sandra Hervas-Stubbs1,2, Aurélie Olivier1,2, Florence Boisgerault1,2, Nathalie Thieblemont3, and Claude Leclerc1,2

1 Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris France; 2 Institut National de la Santé et de la Recherche Médicale (INSERM) U833, Paris, France; 3 Centre National de la Recherche Scientifique (CNRS-UMR 8147), Université Paris Descartes, Faculté le médecine René Descartes, Site Necker, Paris, France

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}/ß 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.


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