Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway

Koji Tamada, Koji Shimozaki, Andrei I. Chapoval, Gefeng Zhu, Gabriel Sica, Dallas Flies, Tom Boone, Hailing Hsu, Yang Xin Fu, Shigekazu Nagata, Jian Ni, Lieping Chen

Research output: Contribution to journalArticlepeer-review

262 Scopus citations

Abstract

LIGHT was recently described as a member of the tumor necrosis factor (TNF) 'superfamily'. We have isolated a mouse homolog of human LIGHT and investigated its immunoregulatory functions in vitro and in vivo. LIGHT has potent, CD28-independent co-stimulatory activity leading to T-cell growth and secretion of gamma interferon and granulocyte-macrophage colony-stimulating factor. Gene transfer of LIGHT induced an antigen-specific cytolytic T-cell response and therapeutic immunity against established mouse P815 tumor. In contrast, blockade of LIGHT by administration of soluble receptor or antibody led to decreased cell-mediated immunity and ameliorated graft-versus-host disease. Our studies identify a previously unknown T-cell co-stimulatory pathway as a potential therapeutic target.

Original languageEnglish (US)
Pages (from-to)283-289
Number of pages7
JournalNature medicine
Volume6
Issue number3
DOIs
StatePublished - Mar 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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