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 Chapoval, Gefeng Zhu, Gabriel Sica, Dallas Flies, Tom Boone, Hailing Hsu, Yang Xin Fu, Shigekazu Nagata, Jian Ni, Lieping Chen

Research output: Contribution to journalArticle

255 Citations (Scopus)

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 1 2000
Externally publishedYes

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T-cells
Graft vs Host Disease
Grafts
Cellular Immunity
Tumors
Modulation
T-Lymphocytes
Light
Neoplasms
Gene transfer
Cell growth
Granulocyte-Macrophage Colony-Stimulating Factor
Interferon-gamma
Immunity
Tumor Necrosis Factor-alpha
Antigens
Antibodies
Therapeutics
Growth
Genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway. / Tamada, Koji; Shimozaki, Koji; Chapoval, Andrei; Zhu, Gefeng; Sica, Gabriel; Flies, Dallas; Boone, Tom; Hsu, Hailing; Fu, Yang Xin; Nagata, Shigekazu; Ni, Jian; Chen, Lieping.

In: Nature Medicine, Vol. 6, No. 3, 01.03.2000, p. 283-289.

Research output: Contribution to journalArticle

Tamada, K, Shimozaki, K, Chapoval, A, Zhu, G, Sica, G, Flies, D, Boone, T, Hsu, H, Fu, YX, Nagata, S, Ni, J & Chen, L 2000, 'Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway', Nature Medicine, vol. 6, no. 3, pp. 283-289. https://doi.org/10.1038/73136
Tamada, Koji ; Shimozaki, Koji ; Chapoval, Andrei ; Zhu, Gefeng ; Sica, Gabriel ; Flies, Dallas ; Boone, Tom ; Hsu, Hailing ; Fu, Yang Xin ; Nagata, Shigekazu ; Ni, Jian ; Chen, Lieping. / Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway. In: Nature Medicine. 2000 ; Vol. 6, No. 3. pp. 283-289.
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