Invariant and Noninvariant Natural Killer T Cells Exert Opposite Regulatory Functions on the Immune Response during Murine Schistosomiasis
- 1 May 2007
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 75 (5), 2171-2180
- https://doi.org/10.1128/iai.01178-06
Abstract
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) α chain (Vα14Jα18 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 Jα18−/−(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.Keywords
This publication has 56 references indexed in Scilit:
- Double-stranded RNAs from the Helminth Parasite Schistosoma Activate TLR3 in Dendritic CellsPublished by Elsevier BV ,2005
- The role of CD1d in the immune response against Listeria infectionCellular Immunology, 2004
- Surface receptors identify mouse NK1.1+ T cell subsets distinguished by function and T cell receptor typeEuropean Journal of Immunology, 2003
- The immunobiology of schistosomiasisNature Reviews Immunology, 2002
- Natural Killer T Cell Ligand α-Galactosylceramide Enhances Protective Immunity Induced by Malaria VaccinesThe Journal of Experimental Medicine, 2002
- DuringTrypanosoma cruziInfection CD1d-Restricted NK T Cells Limit Parasitemia and Augment the Antibody Response to a Glycophosphoinositol-Modified Surface ProteinInfection and Immunity, 2002
- The Mouse Cd1d-Restricted Repertoire Is Dominated by a Few Autoreactive T Cell Receptor FamiliesThe Journal of Experimental Medicine, 2001
- Diverse CD1d-restricted T cells: diverse phenotypes, and diverse functionsSeminars in Immunology, 2000
- Selective induction of NK cell proliferation and cytotoxicity by activated NKT cellsEuropean Journal of Immunology, 2000
- Immunization with α-galactosylceramide polarizes CD1-reactive NK T cells towards Th2 cytokine synthesisEuropean Journal of Immunology, 1999