TY - JOUR
T1 - Critical impact of the kinetics of dendritic cells activation on the in vivo induction of tumor-specific T lymphocytes
AU - Camporeale, Annalisa
AU - Boni, Andrea
AU - Iezzi, Giandomenica
AU - Degl'Innocenti, Elena
AU - Grioni, Matteo
AU - Mondino, Anna
AU - Bellone, Matteo
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Dendritic cells (DCs) need activation for the priming of antigen-specific immune responses. Recently activated Des were described to prime in vitro strong T helper cell type 1 (Th1) responses, whereas at later time points, the same cells preferentially prime Th2 cells [Langenkemp, A. et al., Nat. Immunol. 1: 311-316, 2000]. Because the immune response against cancer strongly depends on CTLs of Th1-like phenotype (Tc1), we verified here whether the kinetics of DCs activation also impacted on in vivo priming of tumor-specific CTLs. After pulsing with the CTL epitope TRP-2180-188, bone-marrow-derived DCs, exposed to lipopolysaccharide (LPS) for 8 h (8hDC), elicited a more powerful Tc1 response in C57BL/6 mice than did untreated DCs, or DCs exposed to LPS for 48 h (48hDC). Indeed, 8hDCs were the most potent protective and therapeutic vaccine against B16 melanoma. Despite a higher expression of MHC and costimulatory molecules by 48hDCs, 8hDCs and 48hDCs showed comparable allostimulatory and migration potential, and susceptibility to CTL-mediated apoptosis. However, 8hDCs exhibited a significantly higher interleukin (IL)-12 production potential. Release of IL-12 was necessary to induce potent Tc1 cells, because DCs from IL-12p40-/- mice, irrespective of their maturation level, generated low CTL responses, comparable with 48hDCs and OhDCs from wild-type animals. Our data are relevant for the design of DC-based vaccines.
AB - Dendritic cells (DCs) need activation for the priming of antigen-specific immune responses. Recently activated Des were described to prime in vitro strong T helper cell type 1 (Th1) responses, whereas at later time points, the same cells preferentially prime Th2 cells [Langenkemp, A. et al., Nat. Immunol. 1: 311-316, 2000]. Because the immune response against cancer strongly depends on CTLs of Th1-like phenotype (Tc1), we verified here whether the kinetics of DCs activation also impacted on in vivo priming of tumor-specific CTLs. After pulsing with the CTL epitope TRP-2180-188, bone-marrow-derived DCs, exposed to lipopolysaccharide (LPS) for 8 h (8hDC), elicited a more powerful Tc1 response in C57BL/6 mice than did untreated DCs, or DCs exposed to LPS for 48 h (48hDC). Indeed, 8hDCs were the most potent protective and therapeutic vaccine against B16 melanoma. Despite a higher expression of MHC and costimulatory molecules by 48hDCs, 8hDCs and 48hDCs showed comparable allostimulatory and migration potential, and susceptibility to CTL-mediated apoptosis. However, 8hDCs exhibited a significantly higher interleukin (IL)-12 production potential. Release of IL-12 was necessary to induce potent Tc1 cells, because DCs from IL-12p40-/- mice, irrespective of their maturation level, generated low CTL responses, comparable with 48hDCs and OhDCs from wild-type animals. Our data are relevant for the design of DC-based vaccines.
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M3 - Article
C2 - 12839960
AN - SCOPUS:0038079749
VL - 63
SP - 3688
EP - 3694
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 13
ER -