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,
Divisions of
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Developmental Immunology and
Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; and
Department of Biology, University of California at San Diego, La Jolla, CA 92037
LIGHT, a member of the TNF family of cytokines (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for herpesvirus entry mediator, a receptor expressed on T cells), is induced on activated T cells and mediates costimulatory and antitumor activity in vitro. Relatively little information is available on the in vivo effects of LIGHT expression, particularly within the T cell compartment. In this work, we describe transgenic mice that express human LIGHT under the control of the CD2 promoter, resulting in constitutive transgene expression in cells of the T lymphocyte lineage. LIGHT-transgenic animals exhibit abnormalities in both lymphoid tissue architecture and the distribution of lymphocyte subsets. They also show signs of inflammation that are most severe in the intestine, along with tissue destruction of the reproductive organs. These LIGHT-mediated effects were recapitulated when immune-deficient mice were reconstituted with bone marrow from LIGHT-transgenic donor mice. T cells in the LIGHT-transgenic mice have an activated phenotype and mucosal T cells exhibit enhanced Th1 cytokine activity. The results indicate that LIGHT may function as an important regulator of T cell activation, and implicate LIGHT signaling pathways in inflammation focused on mucosal tissues.
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R. Castellano, C. Van Lint, V. Peri, E. Veithen, Y. Morel, R. Costello, D. Olive, and Y. Collette Mechanisms Regulating Expression of the Tumor Necrosis Factor-related light Gene. ROLE OF CALCIUM-SIGNALING PATHWAY IN THE TRANSCRIPTIONAL CONTROL J. Biol. Chem., November 1, 2002; 277(45): 42841 - 42851. [Abstract] [Full Text] [PDF]
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G. Shi, H. Luo, X. Wan, T. W. Salcedo, J. Zhang, and J. Wu Mouse T cells receive costimulatory signals from LIGHT, a TNF family member Blood, October 16, 2002; 100(9): 3279 - 3286. [Abstract] [Full Text] [PDF]
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S. Scheu, J. Alferink, T. Potzel, W. Barchet, U. Kalinke, and K. Pfeffer Targeted Disruption of LIGHT Causes Defects in Costimulatory T Cell Activation and Reveals Cooperation with Lymphotoxin {beta} in Mesenteric Lymph Node Genesis J. Exp. Med., June 17, 2002; 195(12): 1613 - 1624. [Abstract] [Full Text] [PDF]
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K. Tamada, J. Ni, G. Zhu, M. Fiscella, B. Teng, J. M. A. van Deursen, and L. Chen Cutting Edge: Selective Impairment of CD8+ T Cell Function in Mice Lacking the TNF Superfamily Member LIGHT J. Immunol., May 15, 2002; 168(10): 4832 - 4835. [Abstract] [Full Text] [PDF]
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Q. Ye, C. C. Fraser, W. Gao, L. Wang, S. J. Busfield, C. Wang, Y. Qiu, A. J. Coyle, J.-C. Gutierrez-Ramos, and W. W. Hancock Modulation of LIGHT-HVEM Costimulation Prolongs Cardiac Allograft Survival J. Exp. Med., March 18, 2002; 195(6): 795 - 800. [Abstract] [Full Text] [PDF]
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