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* Laboratoire d’Immunologie des Tumeurs and
Département d’Hématologie, Institut Paoli-Calmettes, Université de la Méditerranée, Marseille, France;
Institut National de la Santé et la Recherche Médicale Unité 119, Marseille, France; and
Department of Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406
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-1
, or TNF-
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-. 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.
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