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Article
Nature Immunology  4, 1230 - 1237 (2003)
Published online: 26 October 2003; Corrected online: 02 November 2003 | doi:10.1038/ni1002

Mechanism of CD1d-restricted natural killer T cell activation during microbial infection

Manfred Brigl1, Lynn Bry1, 2, Sally C Kent3, Jenny E Gumperz1, 4 & Michael B Brenner1, 4

1  Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

2  Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

3  Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

4  These authors contributed equally to this work.

Correspondence should be addressed to Michael B Brenner mbrenner@rics.bwh.harvard.edu
CD1d-restricted natural killer T (NKT) cells are important for host defense against a variety of microbial pathogens. How and when these T cells become activated physiologically during infection remains unknown. Our data support a model in which NKT cells use a unique activation mechanism not requiring their recognition of microbial antigens. Instead, weak responses to CD1d-presented self antigens were amplified by interleukin 12 made by dendritic cells in response to microbial products, resulting in potent interferon-bold gamma secretion. NKT cells were among the first lymphocytes to respond during Salmonella typhimurium infection, and their activation in vivo also depended on interleukin 12 and CD1d recognition. We propose this mechanism of activation as a major pathway responsible for the rapid activation of NKT cells in different microbial infections.

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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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