Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction

LIGHT, a member of the TNF family of cytokines (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for herp esvirus entry mediator, a receptor expressed on T cells), is induced on act ivated 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 de scribe transgenic mice that express human LIGHT under the control of the CD 2 promoter, resulting in constitutive transgene expression in cells of the T lymphocyte lineage. LIGHT-transgenic animals exhibit abnormalities in bot h 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-medi ated effects were recapitulated when immune-deficient mice were reconstitut ed with bone marrow from LIGHT-transgenic donor mice. T cells in the LIGHT- transgenic mice have an activated phenotype and mucosal T cells exhibit enh anced Th1 cytokine activity. The results indicate that LIGHT may function a s an important regulator of T cell activation, and implicate LIGHT signalin g pathways in inflammation focused on mucosal tissues.