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Infection and Immunity, November 2002, p. 6302-6309, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6302-6309.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Activation of NKT Cells Protects Mice from Tuberculosis

Alissa Chackerian, Jen Alt, Vaji Perera, and Samuel M. Behar*

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

Received 8 April 2002/ Returned for modification 11 June 2002/ Accepted 7 August 2002

The T-cell immune response to Mycobacterium tuberculosis is critical in preventing clinical disease. While it is generally accepted that both major histocompatibility complex class I (MHC-I)-restricted CD8+ and MHC-II-restricted CD4+ T cells are important for the immune response to M. tuberculosis, the role of non-MHC-restricted T cells is still not clearly delineated. We have previously reported that CD1d-/- mice do not differ from CD1d+/+ mice in their survival following infection with M. tuberculosis. We now show that, although CD1d-restricted NKT cells are not required for optimum immunity to M. tuberculosis, specific activation of NKT cells by the CD1d ligand {alpha}-galactosylceramide protects susceptible mice from tuberculosis. Treatment with {alpha}-galactosylceramide reduced the bacterial burden in the lungs, diminished tissue injury, and prolonged survival of mice following inoculation with virulent M. tuberculosis. The capacity of activated NKT cells to stimulate innate immunity and modulate the adaptive immune response to promote a potent antimicrobial immune response suggests that {alpha}-galactosylceramide administration could have a role in new strategies for the therapy of infectious diseases.

* Corresponding author. Mailing address: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Smith Building, Room 516C, 1 Jimmy Fund Way, Boston, MA 02115. Phone: (617) 525-1033. Fax: (617) 525-1010. E-mail: sbehar{at}rics.bwh.harvard.edu.

Editor: S. H. E. Kaufmann

Infection and Immunity, November 2002, p. 6302-6309, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6302-6309.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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