CD160 serves as a negative regulator of NKT cells in acute hepatic injury

Abstract

Abstract CD160 and BTLA binds to herpes virus entry mediator (HVEM). Although the function of BTLA as a negative regulator has been well documented, the role of CD160 in NKT cells remains unclear. Upon analysis of CD160−/−mice and their mixed bone marrow chimeras, we found no apparent developmental defects of NKT cells. However, CD160−/−mice demonstrate severe liver injury after in vivo challenges with α-galactosylceramide (α-GalCer) and a large proportion of CD160−/− mice died following Con A challenges with elevated serum AST and ALT levels, due to hyperactivation of NKT cells with significantly elevated levels of IFN-γ, TNF-α, and IL-4. Importantly, inhibition of BTLA by anti-BTLA mAbs aggravated α-GalCer-induced hepatic injury, highlighting that both CD160 and BTLA serve as non-overlapping negative regulators of NKT cells. Our data presents CD160 as an important co-inhibitory receptor that delivers antigen-dependent signals in NKT cells that dampen cytokine production during early innate immune activation processes.