Abstract
Herpesvirus entry mediator (HVEM), a TNF receptor superfamily member, has been previously described as a T cell costimulatory receptor. Surprisingly, HVEM-/- T cells showed enhanced responses to in vitro concanavalin A (ConA) stimulation when compared with WT T cells. Consistent with these findings, HVEM-/- mice exhibited increased morbidity and mortality as compared with WT mice in a model of ConA-mediated T cell-dependent autoimmune hepatitis. HVEM-/- mice produced higher levels of multiple cytokines, which were dependent on the presence of CD4+ T cells. Furthermore, HVEM-/- mice were more susceptible to MOG peptide-induced experimental autoimmune encephalopathy, and they showed increased T cell proliferation and cytokine production in response to antigen-specific challenge. Taken together, our data revealed an unexpected regulatory role of HVEM in T cell-mediated immune responses and autoimmune diseases.
MeSH terms
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Animals
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Concanavalin A / pharmacology
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Cytokines / blood
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Disease Susceptibility
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Humans
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Liver / cytology
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Liver / metabolism
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Liver / pathology
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Lymphocyte Activation*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism*
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Receptors, Tumor Necrosis Factor, Member 14
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Receptors, Virus / genetics
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Receptors, Virus / metabolism*
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Spleen / cytology
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Spleen / metabolism
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Spleen / pathology
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Survival Rate
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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Tumor Necrosis Factor Ligand Superfamily Member 14
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Cytokines
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Membrane Proteins
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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, human
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TNFSF14 protein, human
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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
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Concanavalin A