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Infection and Immunity, November 2005, p. 7541-7547, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7541-7547.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Invariant NKT Cells Are Essential for the Regulation of Hepatic CXCL10 Gene Expression during Leishmania donovani Infection

Mattias Svensson,1,{dagger} Soombul Zubairi,1,{ddagger} Asher Maroof,1,{ddagger} Fatima Kazi,1 Masaru Taniguchi,2 and Paul M. Kaye1*

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom,1 RIKEN Research Center for Allergy and Immunology, Laboratory for Immune Regulation, Tsurumi, Yokohama 230-0045, Japan2

Received 8 June 2005/ Returned for modification 20 July 2005/ Accepted 25 July 2005

Gamma interferon (IFN-{gamma})-regulated chemokines of the CXC family have been implicated as key regulators of a variety of T-cell-dependent inflammatory processes. However, the cellular source(s) of IFN-{gamma} that regulates their early expression has rarely been defined. Here, we have directly addressed this question in mice after Leishmania donovani infection. Comparison of CXCL10 mRNA accumulation in normal and IFN-{gamma}-deficient mice confirmed an absolute requirement for IFN-{gamma} for sustained (24 h) expression of CXCL10 mRNA accumulation in this model. In normal mice, IFN-{gamma} was produced by both CD3int NK1.1+ NKT cells and CD3 NK1.1+ NK cells, as detected by intracellular flow cytometry. Strikingly, B6.J{alpha}281–/– mice lacking NKT cells that express the invariant V{alpha}14J{alpha}18 T-cell-receptor {alpha} chain, although retaining a significant population of IFN-{gamma}-producing NK cells and NKT cells, were unable to sustain CXCL10 mRNA accumulation. These data indicate that invariant NKT cells are indispensable for the regulation of hepatic CXCL10 gene expression during L. donovani infection.


* Corresponding author. Present address: Immunology and Infection Unit, Department of Biology, University of York, Heslington, York YO10 5YW, United Kingdom. Phone: 441904328840. Fax: 44190432844. E-mail: pmk2{at}york.ac.uk.

Editor: W. A. Petri, Jr.

{dagger} Present address: Center for Infectious Medicine, Department of Medicine, F59, Karolinska Institutet, Karolinska University Hospital, Huddinge, 14186 Stockholm, Sweden.

{ddagger} Present address: Immunology and Infection Unit, Department of Biology, University of York, Heslington, York YO10 5YW, United Kingdom.


Infection and Immunity, November 2005, p. 7541-7547, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7541-7547.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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