Expansion and hyperactivity of CD1d-restricted NKT cells during the progression of systemic lupus erythematosus in (New Zealand Black × New Zealand White)F1 mice

Claire Forestier, Alberto Molano, Jin Seon Im, Yves Dutronc, Betty Diamond, Anne Davidson, Petr A. Illarionov, Gurdyal S. Besra, Steven A. Porcelli

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62 Scopus citations

Abstract

CD1d-restricted NKT cells expressing invariant TCR α-chain rearrangements (iNKT cells) have been reported to be deficient in humans with a variety of autoimmune syndromes and in certain strains of autoimmune mice. In addition, injection of mice with α-galactosylceramide, a specific glycolipid agonist of iNKT cells, activates these T cells and ameliorates autoimmunity in several different disease models. Thus, deficiency and reduced function in iNKT cells are considered to be risk factors for the development of such diseases. In this study we report that the development of systemic lupus erythematosus in (New Zealand Black (NZB) × New Zealand White (NZW))F 1 mice was paradoxically associated with an expansion and activation of iNKT cells. Although young (NZB × NZW)F1 mice had normal levels of iNKT cells, these expanded with age and became phenotypically and functionally hyperactive. Activation of iNKT cells in (NZB × NZW)F 1 mice in vivo or in vitro with α-galactosylceramide indicated that the immunoregulatory role of iNKT cells varied over time, revealing a marked increase in their potential to contribute to production of IFN-γ with advancing age and disease progression. This evolution of iNKT cell function during the progression of autoimmunity may have important implications for the mechanism of disease in this model of systemic lupus erythematosus and for the development of therapies using iNKT cell agonists.

Original languageEnglish (US)
Pages (from-to)763-770
Number of pages8
JournalJournal of Immunology
Volume175
Issue number2
StatePublished - Jul 15 2005

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Forestier, C., Molano, A., Im, J. S., Dutronc, Y., Diamond, B., Davidson, A., Illarionov, P. A., Besra, G. S., & Porcelli, S. A. (2005). Expansion and hyperactivity of CD1d-restricted NKT cells during the progression of systemic lupus erythematosus in (New Zealand Black × New Zealand White)F1 mice. Journal of Immunology, 175(2), 763-770.