Quantitative and qualitative differences in the in vivo response of NKT cells to distinct α- and β-anomeric glycolipids

Vrajesh V. Parekh, Avneesh Singh, Michael T. Wilson, Danyvid Olivares-Villagómez, Jelena S. Bezbradica, Hiroko Inazawa, Hiromi Ehara, Teruyuki Sakai, Isao Serizawa, Lan Wu, Chyung Ru Wang, Sebastian Joyce, Luc Van Kaer

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Abstract

NKT cells represent a unique subset of immunoregulatory T cells that recognize glycolipid Ags presented by the MHC class I-like molecule CD1d. Because of their immunoregulatory properties, NKT cells are attractive targets for the development of immunotherapies. The prototypical NKT cell ligand α-galactosylceramide (α-GalCer), originally isolated from a marine sponge, has potent immunomodulatory activities in mice, demonstrating therapeutic efficacy against metastatic tumors, infections, and autoimmune diseases, but also has a number of adverse side effects. In vivo administration of α-GalCer to mice results in the rapid activation of NKT cells, which is characterized by cytokine secretion, surface receptor down-regulation, expansion, and secondary activation of a variety of innate and adaptive immune system cells. In this study, we have evaluated the in vivo immune response of mice to a set of structural analogues of α-GalCer. Our results show that, contrary to current thinking, β-anomeric GalCer can induce CD1d-dependent biological activities in mice, albeit at lower potency than α-anomeric GalCer. In addition, we show that the response of NKT cells to distinct GalCer differs not only quantitatively, but also qualitatively. These findings indicate that NKT cells can fine-tune their immune responses to distinct glycolipid Ags in vivo, a property that may be exploited for the development of effective and safe NKT cell-based immunotherapies.

Original languageEnglish (US)
Pages (from-to)3693-3706
Number of pages14
JournalJournal of Immunology
Volume173
Issue number6
StatePublished - Sep 15 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Parekh, V. V., Singh, A., Wilson, M. T., Olivares-Villagómez, D., Bezbradica, J. S., Inazawa, H., Ehara, H., Sakai, T., Serizawa, I., Wu, L., Wang, C. R., Joyce, S., & Van Kaer, L. (2004). Quantitative and qualitative differences in the in vivo response of NKT cells to distinct α- and β-anomeric glycolipids. Journal of Immunology, 173(6), 3693-3706.