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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1734-1741.
Prepublished online as a Blood First Edition Paper on May 17, 2005; DOI 10.1182/blood-2004-10-3991.


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Submitted October 15, 2004
Accepted May 9, 2005

Efficient migration of dendritic cells towards lymph node chemokines and induction of Th1 responses require maturation stimulus and apoptotic cells interaction

Nicolas Bertho*, Henri Adamski, Louis Toujas, Martine Debove, Jean Davoust, and Veronique Quillien

Centre Eugene Marquis, Departement de Biologie, Rennes I University, Rennes, France
Department of Dermatologie, Faculte de Rennes, Rennes, France
EFS Bretagne, Rennes, France
Immunology, Genethon/Centre National de la Recherche Scientifique (CNRS) Unite Mixte de Recherche (UMR), Evry, France

* Corresponding author; email: bertho{at}genethon.fr.

Dendritic cells (DC) have the unique ability to initiate primary immune responses and can be conditioned for vaccinal purposes, to present antigens after the engulfment of apoptotic cells. To recruit the rare antigen-specific naive T cells, DC require a maturation step and their subsequent transport towards lymph node (LN). To date, prostaglandin E2 (PGE2) is the best-characterized compound inducing this LN directed migration in vitro, but PGE2 may skew the immune responses towards a Th2 direction. We demonstrate here that upon incubation with apoptotic tumor cells and TNF{alpha} or LPS, human monocyte-derived DC become fully mature and acquire high migratory capacities towards LN directing chemokines. The migration of TNF-{alpha} treated DC occurs only after co-treatment with apoptotic cells, but not with necrotic cells. DC migration requires CD36 expression and incubation with apoptotic cells in the presence of heat labile serum components. Moreover, upon treatment with apoptotic cells and LPS, the migrating DC are able to recruit naive T cells to generate Th1 immune responses. Our results show that co-treatments of DC with apoptotic tumor cells and inflammatory signals are promising for the design of anti-tumoral DC based vaccine.


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