title: Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction.
abstract: 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.
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Shaikh
authors.forename: S
authors.initials: S
authors.lastname: Santee
authors.forename: S W
authors.initials: SW
authors.lastname: Granger
authors.forename: K
authors.initials: K
authors.lastname: Butrovich
authors.forename: T
authors.initials: T
authors.lastname: Cheung
authors.forename: M
authors.initials: M
authors.lastname: Kronenberg
authors.forename: H
authors.initials: H
authors.lastname: Cheroutre
authors.forename: C F
authors.initials: CF
authors.lastname: Ware
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D007247:Infertility, Female / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D053259:Lymphotoxin beta Receptor; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism
chemical_list: C505697:LTBR protein, human; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; C505914:TNFSF14 protein, human; C506029:Tnfrsf14 protein, mouse; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha