Abstract
Negative selection serves as a major mechanism to maintain self-tolerance. We previously reported that LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor), a TNF family member, plays an important role in thymocyte development via promoting apoptosis of double-positive thymocytes. Here, we demonstrated that LIGHT-mediated deletion of thymocyte requires the strong interaction of TCR with MHC/self-peptide. Transgenic mice overexpressing LIGHT in thymocytes were bred with a transgenic mouse line expressing a TCR recognizing the H-Y male Ag in the context of H-2b class I MHC molecules. In male H-Y/LIGHT double-transgenic mice, more efficient negative selection of H-Y T cells occurred, and total thymocyte number was further reduced compared with H-Y/negative littermates. In contrast, the presence of LIGHT transgene had no evident impact on the thymocyte development of female H-Y/LIGHT double-transgenic mice. Taken together, LIGHT plays a role in negative selection of thymocytes via inducing the apoptosis of thymocytes bearing high affinity TCR during negative selection.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / genetics
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Apoptosis / immunology
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Autoantigens / biosynthesis
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Autoantigens / genetics
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Autoantigens / metabolism*
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Clonal Deletion / immunology*
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Epitopes, T-Lymphocyte / metabolism
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Female
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H-Y Antigen / biosynthesis
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H-Y Antigen / genetics
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H-Y Antigen / metabolism*
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Ligands
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Lymphotoxin beta Receptor
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Male
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Proteins / physiology*
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Transgenic
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Receptors, Antigen, T-Cell / metabolism*
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor / physiology
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Receptors, Tumor Necrosis Factor, Member 14
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Receptors, Virus / metabolism
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Sex Characteristics
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Thymus Gland / cytology*
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Thymus Gland / immunology*
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Thymus Gland / metabolism
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Tumor Necrosis Factor Ligand Superfamily Member 14
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / physiology*
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Autoantigens
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Epitopes, T-Lymphocyte
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H-Y Antigen
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Ligands
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Ltbr protein, mouse
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Lymphotoxin beta Receptor
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Membrane Proteins
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Receptors, Antigen, T-Cell
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 14
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Receptors, Virus
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Tnfrsf14 protein, mouse
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Tnfsf14 protein, mouse
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Tumor Necrosis Factor Ligand Superfamily Member 14
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Tumor Necrosis Factor-alpha