PMID- 22688982 OWN - NLM STAT- MEDLINE DCOM- 20130729 LR - 20201226 IS - 0717-6287 (Electronic) IS - 0716-9760 (Linking) VI - 45 IP - 1 DP - 2012 TI - Human dendritic cells sequentially matured with CD4(+) T cells as a secondary signal favor CTL and long-term T memory cell responses. PG - 33-43 LID - S0716-97602012000100005 [pii] LID - 10.4067/S0716-97602012000100005 [doi] AB - Dendritic cells (DCs) are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL) responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-alpha/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-gamma. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy. FAU - Simon, Thomas AU - Simon T AD - Institut de Recherche Therapeutique, Universite de Nantes, Nantes, France. marc.gregoire@nantes.inserm.fr FAU - Tanguy-Royer, Severine AU - Tanguy-Royer S FAU - Royer, Pierre-Joseph AU - Royer PJ FAU - Boisgerault, Nicolas AU - Boisgerault N FAU - Frikeche, Jihane AU - Frikeche J FAU - Fonteneau, Jean-Francois AU - Fonteneau JF FAU - Gregoire, Marc AU - Gregoire M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biol Res JT - Biological research JID - 9308271 RN - 0 (CD4 Antigens) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - CD4 Antigens/*analysis MH - CD4-Positive T-Lymphocytes/*immunology MH - Cells, Cultured MH - Dendritic Cells/cytology/*immunology MH - Humans MH - Immunologic Memory/*immunology MH - Immunophenotyping MH - Immunotherapy MH - Interferon-gamma/immunology MH - Lymphocyte Activation MH - T-Lymphocytes, Cytotoxic/*immunology MH - T-Lymphocytes, Helper-Inducer/*immunology MH - Tumor Necrosis Factor-alpha/immunology EDAT- 2012/06/13 06:00 MHDA- 2013/07/31 06:00 CRDT- 2012/06/13 06:00 PHST- 2011/06/09 00:00 [received] PHST- 2011/11/10 00:00 [accepted] PHST- 2012/06/13 06:00 [entrez] PHST- 2012/06/13 06:00 [pubmed] PHST- 2013/07/31 06:00 [medline] AID - S0716-97602012000100005 [pii] AID - 10.4067/S0716-97602012000100005 [doi] PST - ppublish SO - Biol Res. 2012;45(1):33-43. doi: 10.4067/S0716-97602012000100005.