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

doi:10.1038/73136

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 journal › Article › peer-review

278 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 language	English (US)
Pages (from-to)	283-289
Number of pages	7
Journal	Nature medicine
Volume	6
Issue number	3
DOIs	https://doi.org/10.1038/73136
State	Published - Mar 2000

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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

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.",

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

note = "Funding Information: Acknowledgments We thank K. Jensen for editing this manuscript. This work was supported in part by the Mayo Foundation, by National Institutes of Health grants CA79915 and CA15083 (Mayo Clinic Cancer Center Developmental Fund) to L.C., by grants-in-aid from the Ministry of Education, Science, Sports and Culture in Japan to S.N. and by National Institutes of Health grant HD73104 to Y.F. K.S. is a recipient of a PhD student fellowship from the Japan Society for the Promotion of Science. G.Z. is supported by National Institutes of Health postdoctoral fellow training grant CA09127. The access number for the mouse LIGHT sequence in GenBank is AF123385.",

year = "2000",

month = mar,

doi = "10.1038/73136",

language = "English (US)",

volume = "6",

pages = "283--289",

journal = "Nature medicine",

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AU - Tamada, Koji

AU - Shimozaki, Koji

AU - Chapoval, Andrei I.

AU - Zhu, Gefeng

AU - Sica, Gabriel

AU - Flies, Dallas

AU - Boone, Tom

AU - Hsu, Hailing

AU - Fu, Yang Xin

AU - Nagata, Shigekazu

AU - Ni, Jian

AU - Chen, Lieping

N1 - Funding Information: Acknowledgments We thank K. Jensen for editing this manuscript. This work was supported in part by the Mayo Foundation, by National Institutes of Health grants CA79915 and CA15083 (Mayo Clinic Cancer Center Developmental Fund) to L.C., by grants-in-aid from the Ministry of Education, Science, Sports and Culture in Japan to S.N. and by National Institutes of Health grant HD73104 to Y.F. K.S. is a recipient of a PhD student fellowship from the Japan Society for the Promotion of Science. G.Z. is supported by National Institutes of Health postdoctoral fellow training grant CA09127. The access number for the mouse LIGHT sequence in GenBank is AF123385.

PY - 2000/3

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N2 - 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.

AB - 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.

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

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