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

K Tamada1, K Shimozaki, A I Chapoval

  • 1Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, Minnesota 55905, USA.

Nature Medicine
|March 4, 2000
PubMed

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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