Glycolipid antigen induces long-term natural killer T cell anergy in mice

Vrajesh V. Parekh, Michael T. Wilson, Danyvid Olivares-Villagómez, Avneesh Singh, Lan Wu, Chyung Ru Wang, Sebastian Joyce, Luc Van Kaer

Research output: Contribution to journalArticle

Abstract

Natural killer T (NKT) cells recognize glycolipid antigens presented by the MHC class I-related glycoprotein CD1d. The in vivo dynamics of the NKT cell population in response to glycolipid activation remain poorly understood. Here, we show that a single administration of the synthetic glycolipid α-galactosylceramide (α-GalCer) induces long-term NKT cell unresponsiveness in mice. NKT cells failed to proliferate and produce IFN-γ upon α-GalCer restimulation but retained the capacity to produce IL-4. Consequently, we found that activation of anergic NKT cells with α-GalCer exacerbated, rather than prevented, B16 metastasis formation, but that these cells retained their capacity to protect mice against experimental autoimmune encephalomyelitis. NKT cell anergy was induced in a thymus-independent manner and maintained in an NKT cell-autonomous manner. The anergic state could be broken by IL-2 and by stimuli that bypass proximal TCR signaling events. Collectively, the kinetics of initial NKT cell activation, expansion, and induction of anergy in response to α-GalCer administration resemble the responses of conventional T cells to strong stimuli such as superantigens. Our findings have important implications for the development of NKT cell-based vaccines and immunotherapies.

Original languageEnglish (US)
Pages (from-to)2572-2583
Number of pages12
JournalJournal of Clinical Investigation
Volume115
Issue number9
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

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Natural Killer T-Cells
Glycolipids
Antigens
Galactosylceramides
Superantigens
Autoimmune Experimental Encephalomyelitis
Interleukin-4
Immunotherapy
Thymus Gland
Interleukin-2
Glycoproteins
Vaccines
Neoplasm Metastasis
T-Lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Parekh, V. V., Wilson, M. T., Olivares-Villagómez, D., Singh, A., Wu, L., Wang, C. R., ... Van Kaer, L. (2005). Glycolipid antigen induces long-term natural killer T cell anergy in mice. Journal of Clinical Investigation, 115(9), 2572-2583. https://doi.org/10.1172/JCI24762

Glycolipid antigen induces long-term natural killer T cell anergy in mice. / Parekh, Vrajesh V.; Wilson, Michael T.; Olivares-Villagómez, Danyvid; Singh, Avneesh; Wu, Lan; Wang, Chyung Ru; Joyce, Sebastian; Van Kaer, Luc.

In: Journal of Clinical Investigation, Vol. 115, No. 9, 01.09.2005, p. 2572-2583.

Research output: Contribution to journalArticle

Parekh, VV, Wilson, MT, Olivares-Villagómez, D, Singh, A, Wu, L, Wang, CR, Joyce, S & Van Kaer, L 2005, 'Glycolipid antigen induces long-term natural killer T cell anergy in mice', Journal of Clinical Investigation, vol. 115, no. 9, pp. 2572-2583. https://doi.org/10.1172/JCI24762
Parekh VV, Wilson MT, Olivares-Villagómez D, Singh A, Wu L, Wang CR et al. Glycolipid antigen induces long-term natural killer T cell anergy in mice. Journal of Clinical Investigation. 2005 Sep 1;115(9):2572-2583. https://doi.org/10.1172/JCI24762
Parekh, Vrajesh V. ; Wilson, Michael T. ; Olivares-Villagómez, Danyvid ; Singh, Avneesh ; Wu, Lan ; Wang, Chyung Ru ; Joyce, Sebastian ; Van Kaer, Luc. / Glycolipid antigen induces long-term natural killer T cell anergy in mice. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 9. pp. 2572-2583.
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