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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Research Article Immunology

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 11

Impact of E. coli–induced iNKT cell hyporesponsiveness on the therapeutic activities of α-GalCer.

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Impact of E. coli–induced iNKT cell hyporesponsiveness on the therapeuti...
(A) Determination of B16 tumor lung metastasis formation. B6 mice were left untreated or injected with bacteria, and, 4 weeks later, mice were challenged i.v. with 3 × 105 syngeneic B16 melanoma cells and treated with α-GalCer (5 μg/injection) or vehicle at 0, 4, and 8 days after tumor challenge. Mice were sacrificed after 15 days, and the number of metastatic nodules in the lungs counted. Results shown are the mean ± SEM of 2 experiments with 4 mice in each group per experiment. (B) Determination of EAE. B6 mice were treated with heat-killed E. coli, and, 3 weeks later, mice were immunized with MOG35–55 peptide for induction of EAE, treated with α-GalCer (5 μg/injection) or vehicle on days 0, 4, and 7, and followed for clinical signs of EAE. Results shown are 1 representative experiment of 2 with 5–6 mice in each group.