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.
Highlights
CD160 and BTLA both bind to herpes virus entry mediator
The best-characterized population is a natural killer T (NKT) set composed of αβ T cells specific for microbial lipids presented by the MHC class Ilike CD1d molecule, which is expressed on antigen-presenting cells (APCs) including dendritic cells (DCs) and Kupffer cells (KC)[16]
There was no specific upregulation in other co-stimulatory or coinhibitory receptors on NKT cells, including BTLA, herpes virus entry mediator (HVEM), 41BB, PD-1, OX40, CD28, CTLA-4, and CD95 (Fig. 1c and Supplementary Fig. 1)
Summary
CD160 and BTLA both bind to herpes virus entry mediator. a negative regulatory function of BTLA in natural killer T (NKT) cell activation has been reported, whether CD160 is involved is unclear. We first analyzed the surface expression of CD160 on NKT cells isolated from the thymus, liver, and spleen of C57BL/6 mice by flow cytometry. In an in vivo challenge of C57BL/6 mice with α-GalCer, the percentage of CD160+ NKT cells increased from 5.0 ± 1.5% to 61.2 ± 7.7% in the liver and from 11.51 ± 1.9 to 47.7 ± 3.7% in the spleen within 4 h, with significantly increased MFI (Fig. 1a).
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