The TNF superfamily members LIGHT and CD154 (CD40 ligand) costimulate induction of dendritic cell maturation and elicit specific CTL activity.
LIGHT is a recently identified member of the TNF superfamily that is up-regulated upon activation of T cells. Herpesvirus entry mediator, one of its receptors, is constitutively expressed on immature dendritic cells (DCs). In this report, we demonstrate that LIGHT induces partial DC maturation as demonstrated by Ag presentation and up-regulation of adhesion and costimulatory molecules. LIGHT-stimulated DCs show reduced macropinocytosis and enhanced allogeneic stimulatory capacity but fail to produce significant amounts of IL-12, IL-6, IL-1beta, or TNF-alpha compared with unstimulated DCs. However, LIGHT cooperates with CD154 (CD40 ligand) in DC maturation, with particular potentiation of allogeneic T cell proliferation and cytokine secretion of IL-12, IL-6, and TNF-alpha. Moreover, LIGHT costimulation allows DCs to prime in vitro-enhanced specific CTL responses. Our results suggest that LIGHT plays an important role in DC-mediated immune responses by regulating CD154 signals and represents a potential tool for DC-based cancer immunotherapy.
Morel
Y
Y
Laboratoire d'Immunologie des Tumeurs and Département d'Hématologie, Institut Paoli-Calmettes, Université de la Méditerranée, Marseille, France.
Truneh
A
A
Sweet
R W
RW
Olive
D
D
Costello
R T
RT
D000818:Animals; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000628:therapy; D010873:Pinocytosis; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000276:immunology; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; C505914:TNFSF14 protein, human; C506029:Tnfrsf14 protein, mouse; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma