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Infection and Immunity, May 2007, p. 2171-2180, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01178-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Invariant and Noninvariant Natural Killer T Cells Exert Opposite Regulatory Functions on the Immune Response during Murine Schistosomiasis

Thierry Mallevaey,^1, Josette Fontaine,¹ Laetitia Breuilh,¹ Christophe Paget,¹ Alexandre Castro-Keller,^2,3 Catherine Vendeville,¹ Monique Capron,¹ Maria Leite-de-Moraes,^2,3 François Trottein,^1*, and Christelle Faveeuw^1,

Institut National de la Recherche Médicale, U547, Institut Pasteur de Lille, Institut Fédératif de Recherche 142, Université de Lille 2, Lille F-59019, France,¹ Centre National de la Recherche Scientifique, UMR 8147, Institut Fédératif de Recherche Necker Enfants, Paris F-75015, France,² Hôpital Necker, Paris F-75015, France³

Received 27 July 2006/ Returned for modification 7 September 2006/ Accepted 28 February 2007

CD1d-restricted natural killer T (NKT) cells represent a heterogeneous population of innate memory immune cells expressing both NK and T-cell markers distributed into two major subsets, i.e., invariant NKT (iNKT) cells, which express exclusively an invariant T-cell receptor (TCR) chain (V14J18 in mice), and non-iNKT cells, which express more diverse TCRs. NKT cells quickly produce Th1- and/or Th2-type cytokines following stimulation with glycolipid antigen (Ag) and, through this property, play potent immunoregulatory roles in autoimmune diseases, cancer, and infection. No study has addressed the role of NKT cells in metazoan parasite infections so far. We show that during murine schistosomiasis, the apparent frequency of both iNKT cells and non-iNKT cells decreased in the spleen as early as 3 weeks postinfection (p.i.) and that both populations expressed a greater amount of the activation marker CD69 at 6 weeks p.i., suggesting an activated phenotype. Two different NKT-cell-deficient mouse models, namely, TCR J18^–/– (exclusively deficient in iNKT cells) and CD1d^–/– (deficient in both iNKT and non-iNKT cells) mice, were used to explore the implication of these subsets in infection. We show that whereas both iNKT and non-iNKT cells do not have a major impact on the immune response during the early phase (1 and 4 weeks) of infection, they exert important, although opposite, effects on the immune response during the acute phase of the disease (7 and 12 weeks), after schistosome egg production. Indeed, iNKT cells contribute to Th1 cell differentiation whereas non-iNKT cells might be mostly implicated in Th2 cell differentiation in response to parasite Ag. Our findings suggest, for the first time, that helminths activate both iNKT and non-iNKT cells in vivo, enabling them to differentially influence the Th1/Th2 balance of the immune response.

Published ahead of print on 12 March 2007.

Editor: J. F. Urban, Jr.

Present address: Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, Denver, CO.

F.T. and C.F. contributed equally to this work.

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