How NKT cells detect microorganisms

Honey, Karen

doi:10.1038/nri1616

Research Highlight
Published: 20 April 2005

Natural killer T cells

How NKT cells detect microorganisms

Karen Honey

Nature Reviews Immunology volume 5, page 359 (2005)Cite this article

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Previous studies have shown that Vα14⁺ NKT cells are activated during microbial infection; however, it is controversial whether these cells are activated directly, by TCR recognition of CD1d-presented microbial antigens, or indirectly, by other immune cells responding to the pathogen, so the two research groups set out to investigate this issue. Kinjo et al. showed that presentation by CD1d of two distinct glycosphingolipid mixtures (GSL-1 and GSL-1′) that were purified from Sphingomonas spp., as well as CD1d presentation of GSL-1′sA and GSL-1′sB (which are synthetic versions of individual components of GSL-1′), stimulated cytokine production by both human Vα24⁺ T-cell lines and mouse Vα14⁺ NKT cells but not by mouse T cells lacking the semi-invariant Vα14–Jα18 TCR α-chain. In addition, GSL-1′sA-loaded CD1d multimers bound all of the human Vα24⁺ T cells and a proportion of liver mononuclear cells from wild-type mice, but they did not bind cells from mice that lack Jα18.

Activation of Vα14⁺ NKT cells in the liver was also observed when wild-type mice were immunized with bone-marrow-derived dendritic cells pulsed with either GSL-1′sA or live Sphingomonas yanoikuyae (also known as Sphingobium yanoikuyae), and this in vivo activation did not depend on Toll-like receptor (TLR) activation of these antigen-presenting cells (APCs) or on APC secretion of interleukin-12. Functionally, in vivo Vα14⁺ NKT-cell activation was associated with bacterial clearance.

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ORIGINAL RESEARCH PAPERS

Kinjo, Y. et al. Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434, 520–525 (2005)
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Mattner, J. et al. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434, 525–529 (2005)
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