Abstract
CD160 and BTLA both bind to herpes virus entry mediator. Although a negative regulatory function of BTLA in natural killer T (NKT) cell activation has been reported, whether CD160 is also involved is unclear. By analyzing CD160-/- mice and mixed bone marrow chimeras, we show that CD160 is not essential for NKT cell development. However, CD160-/- mice exhibit severe liver injury after in vivo challenge with α-galactosylceramide (α-GalCer). Moreover, CD160-/- mice are more susceptible to Concanavalin A challenge, and display elevated serum AST and ALT levels, hyperactivation of NKT cells, and enhanced IFN-γ, TNF, and IL-4 production. Lastly, inhibition of BTLA by anti-BTLA mAb aggravates α-GalCer-induced hepatic injury in CD160-/- mice, suggesting that both CD160 and BTLA serve as non-overlapping negative regulators of NKT cells. Our data thus implicate CD160 as a co-inhibitory receptor that delivers antigen-dependent signals in NKT cells to dampen cytokine production during early innate immune activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Chemical and Drug Induced Liver Injury / etiology
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Chemical and Drug Induced Liver Injury / genetics
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Chemical and Drug Induced Liver Injury / metabolism*
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Concanavalin A / administration & dosage
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Concanavalin A / toxicity
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Cytokines / metabolism
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GPI-Linked Proteins / genetics
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GPI-Linked Proteins / metabolism
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Galactosylceramides / administration & dosage
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Galactosylceramides / toxicity
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Liver / drug effects
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Liver / immunology
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Liver / metabolism*
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Mice, Inbred C57BL
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Mice, Knockout
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Natural Killer T-Cells / immunology
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Natural Killer T-Cells / metabolism*
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Receptors, Tumor Necrosis Factor, Member 14 / metabolism
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Survival Analysis
Substances
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Antigens, CD
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BTLA protein, mouse
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Cd160 protein, mouse
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Cytokines
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GPI-Linked Proteins
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Galactosylceramides
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Receptors, Immunologic
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Receptors, Tumor Necrosis Factor, Member 14
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Tnfrsf14 protein, mouse
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alpha-galactosylceramide
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Concanavalin A