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The Journal of Immunology, 2000, 164: 4105-4110.
Copyright © 2000 by The American Association of Immunologists

LIGHT, a TNF-Like Molecule, Costimulates T Cell Proliferation and Is Required for Dendritic Cell-Mediated Allogeneic T Cell Response1

Koji Tamada2,*, Koji Shimozaki2,{dagger}, Andrei I. Chapoval*, Yifan Zhai{ddagger}, Jeffery Su{ddagger}, Su-Fang Chen{ddagger}, Shie-Liang Hsieh§, Shigekazu Nagata{dagger}, Jian Ni{ddagger} and Lieping Chen3,*

* Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905; {dagger} Department of Genetics, Osaka University Medical School, Osaka, Japan; {ddagger} Human Genome Sciences, Inc., Rockville, MD 20850; and § Department of Microbiology and Immunology, National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China

LIGHT is a recently identified member of the TNF superfamily and its receptors, herpesvirus entry mediator and lymphotoxin ß receptor, are found in T cells and stromal cells. In this study, we demonstrate that LIGHT is selectively expressed on immature dendritic cells (DCs) generated from human PBMCs. In contrast, LIGHT is not detectable in DCs either freshly isolated from PBMCs or rendered mature in vitro by LPS treatment. Blockade of LIGHT by its soluble receptors, lymphotoxin ß receptor-Ig or HVEM-Ig, inhibits the induction of DC-mediated primary allogeneic T cell response. Furthermore, engagement of LIGHT costimulates human T cell proliferation, amplifies the NF-{kappa}B signaling pathway, and preferentially induces the production of IFN-{gamma}, but not IL-4, in the presence of an antigenic signal. Our results suggest that LIGHT is a costimulatory molecule involved in DC-mediated cellular immune responses.




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