PMID- 15899913 OWN - NLM STAT- MEDLINE DCOM- 20050929 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 106 IP - 5 DP - 2005 Sep 1 TI - Efficient migration of dendritic cells toward lymph node chemokines and induction of T(H)1 responses require maturation stimulus and apoptotic cell interaction. PG - 1734-41 AB - Dendritic cells (DCs) have the unique ability to initiate primary immune responses, and they can be conditioned for vaccinal purposes to present antigens after the engulfment of apoptotic cells. To recruit the rare antigen-specific naive T cells, DCs require a maturation step and subsequent transport toward 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 in a T(H)2 direction. We demonstrate here that on incubation with apoptotic tumor cells and tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS), human monocyte-derived DCs become fully mature and acquire high migratory capacities toward LN-directing chemokines. The migration of TNF-alpha-treated DCs occurs only after cotreatment 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, on treatment with apoptotic cells and LPS, the migrating DCs are able to recruit naive T cells to generate T(H)1 immune responses. Our results show that the cotreatment of DCs with apoptotic tumor cells and inflammatory signals is promising for the design of an antitumoral DC-based vaccine. FAU - Bertho, Nicolas AU - Bertho N AD - Immunology Department, UMR8115 Genethon BP60, 1 bis rue de l'Internationale, 91002 Evry Cedex, France. bertho@genethon.fr FAU - Adamski, Henri AU - Adamski H FAU - Toujas, Louis AU - Toujas L FAU - Debove, Martine AU - Debove M FAU - Davoust, Jean AU - Davoust J FAU - Quillien, Veronique AU - Quillien V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050517 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Apolipoproteins C) RN - 0 (Chemokines, CC) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Apolipoproteins C/pharmacology MH - Apoptosis/*immunology MH - Cell Communication/immunology MH - Cell Differentiation/immunology MH - Cell Line, Tumor MH - Cell Movement/drug effects/*immunology MH - Cell Polarity/drug effects/immunology MH - Chemokines, CC/*immunology/pharmacology MH - Dendritic Cells/drug effects/*immunology MH - Dinoprostone/pharmacology MH - Humans MH - Lipopolysaccharides/pharmacology MH - Lymph Nodes/cytology/*immunology MH - Phenotype MH - Structure-Activity Relationship MH - T-Lymphocytes/drug effects/immunology MH - Th1 Cells/*immunology MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 2005/05/19 09:00 MHDA- 2005/09/30 09:00 CRDT- 2005/05/19 09:00 PHST- 2005/05/19 09:00 [pubmed] PHST- 2005/09/30 09:00 [medline] PHST- 2005/05/19 09:00 [entrez] AID - S0006-4971(20)53081-4 [pii] AID - 10.1182/blood-2004-10-3991 [doi] PST - ppublish SO - Blood. 2005 Sep 1;106(5):1734-41. doi: 10.1182/blood-2004-10-3991. Epub 2005 May 17.