The Journal of Experimental Medicine
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Published 4 October 2004. doi:10.1084/jem.20040704
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 7, 895-904
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A Subset of Liver NK T Cells Is Activated during Leishmania donovani Infection by CD1d-bound Lipophosphoglycan

Joseph L. Amprey1,2, Jin S. Im2, Salvatore J. Turco3, Henry W. Murray1, Petr A. Illarionov4, Gurdyal S. Besra4, Steven A. Porcelli2, and Gerald F. Späth5

1 Department of Medicine, Weill College of Medicine, Cornell University, New York, NY 10021
2 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461
3 Department of Biochemistry, University of Kentucky, Lexington, KY 40356
4 School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, England, UK
5 Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010

Address correspondence to Gerald Späth, Dept. of Medical and Molecular Parasitology, New York University School of Medicine, 341 E. 25th St., New York, NY 10010. Phone: (212) 263-6763; Fax: (212) 263-8116; email: spaetg01{at}med.nyu.edu

Natural killer (NK) T cells are activated by synthetic or self-glycolipids and implicated in innate host resistance to a range of viral, bacterial, and protozoan pathogens. Despite the immunogenicity of microbial lipoglycans and their promiscuous binding to CD1d, no pathogen-derived glycolipid antigen presented by this pathway has been identified to date. In the current work, we show increased susceptibility of NK T cell–deficient CD1d–/– mice to Leishmania donovani infection and Leishmania-induced CD1d-dependent activation of NK T cells in wild-type animals. The elicited response was Th1 polarized, occurred as early as 2 h after infection, and was independent from IL-12. The Leishmania surface glycoconjugate lipophosphoglycan, as well as related glycoinositol phospholipids, bound with high affinity to CD1d and induced a CD1d-dependent IFN{gamma} response in naive intrahepatic lymphocytes. Together, these data identify Leishmania surface glycoconjugates as potential glycolipid antigens and suggest an important role for the CD1d–NK T cell immune axis in the early response to visceral Leishmania infection.

Key Words: Trypanosomatidae • glycoconjugates • CD1d antigen • natural immunity


J.L. Amprey and J.S. Im contributed equally to this work.

Abbreviations used in this paper: {alpha}GC, {alpha}-galactosylceramide; GIPL, glycoinositol phospholipid; iNK, invariant NK; LPG, lipophosphoglycan.


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