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

Nature Medicine volume 6, pages 283–289 (2000)Cite this article

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.

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Figure 1: Amino-acid sequence and expression of mouse LIGHT.
Figure 2: Co-stimulatory activity of mouse LIGHT.
Figure 3: Induction of immunity by LIGHT gene transfer against P815 tumor.
Figure 4: Amelioration of GVHD by injection of LTβR–Ig.
Figure 5: Inhibition of alloreactive CTL induction by blockade of LIGHT pathway.
Figure 6: Cytokine production by modulation of LIGHT co-stimulatory pathway.

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Acknowledgements

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.

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Authors and Affiliations

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

    Koji Tamada, Andrei I. Chapoval, Gefeng Zhu, Gabriel Sica, Dallas Flies & Lieping Chen

  2. Department of Genetics, Osaka University Medical School, Osaka, Japan

    Koji Shimozaki & Shigekazu Nagata

  3. Amgen, Thousand Oaks, 91320, California , USA

    Tom Boone & Hailing Hsu

  4. Department of Pathology, University of Chicago, Chicago, USA, 60637, Ilinois

    Yang-Xin Fu

  5. Human Genome Sciences, Inc, Rockville, 20850, Maryland, USA

    Jian Ni

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Correspondence to Jian Ni or Lieping Chen.

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Tamada, K., Shimozaki, K., Chapoval, A. et al. Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway. Nat Med 6, 283–289 (2000). https://doi.org/10.1038/73136

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