Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice
Sungjune Kim, … , Lan Wu, Luc Van Kaer
Sungjune Kim, … , Lan Wu, Luc Van Kaer
Published May 1, 2008
Citation Information: J Clin Invest. 2008;118(6):2301-2315. https://doi.org/10.1172/JCI33071.
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Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice

Abstract

Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize glycolipid antigens in the context of the MHC class I–like antigen-presenting molecule CD1d. In vivo activation of mouse iNKT cells with the glycolipid α-galactosylceramide (α-GalCer) results in the acquisition of a hyporesponsive (anergic) phenotype by these cells. Because iNKT cells can become activated in the context of infectious agents, here we evaluated whether iNKT cell activation by microorganisms can influence subsequent responses of these cells to glycolipid antigen stimulation. We found that mouse iNKT cells activated in vivo by multiple bacterial microorganisms, or by bacterial LPS or flagellin, became unresponsive to subsequent activation with α-GalCer. This hyporesponsive phenotype of iNKT cells required IL-12 expression and was associated with changes in the surface phenotype of these cells, reduced severity of concanavalin A–induced hepatitis, and alterations in the therapeutic activities of α-GalCer. These findings may have important implications for the development of iNKT cell–based therapies.

Authors

Sungjune Kim, Saif Lalani, Vrajesh V. Parekh, Tiffaney L. Vincent, Lan Wu, Luc Van Kaer

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Figure 1

Multiple bacterial microorganisms activate murine iNKT cells, resulting in hyporesponsiveness of splenocytes to subsequent in vitro challenge with α-GalCer (αGC).

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Multiple bacterial microorganisms activate murine iNKT cells, resulting ...
In vivo response of mice to treatment with heat-killed or live bacteria at day 1 (A) or week 3 (B). Mice were injected with α-GalCer (5 μg/mouse, i.p.) or with the indicated heat-killed or live bacteria (i.v.) and sacrificed at day 1 or week 3, and spleen or liver mononuclear cells were prepared and stained with anti–TCR-β–FITC, anti-CD69–FITC, anti-NK1.1–PE, anti-B220–PerCP, and CD1d-tetramer–APC and analyzed by flow cytometry. Numbers indicate the percentage of TCR-β+tetramer+ cells among B220– cells or the percentage of NK1.1– cells among iNKT cells. The shaded areas represent the staining of naive iNKT cells, and the solid lines represent the staining of iNKT cells from mice treated with α-GalCer or bacteria. Representative plots from 4–8 mice per group are shown. LM, L. monocytogenes.