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Infection and Immunity, July 2004, p. 3759-3768, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3759-3768.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Limited Antigen-Specific Cellular Response Is Sufficient for the Early Control of Mycobacterium tuberculosis in the Lung but Is Insufficient for Long-Term Survival

Joanne Turner,1* Karen M. Dobos,1 Marc A Keen,1 Anthony A. Frank,1 Stefan Ehlers,2 Ian M. Orme,1 John T. Belisle,1 and Andrea M. Cooper3

Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80523,1 Division of Molecular Infection Biology, Research Center Borstel, Center for Medicine and Biosciences, D-23845 Borstel, Germany,2 Trudeau Institute, Saranac Lake, New York 129833

Received 25 November 2003/ Returned for modification 13 February 2004/ Accepted 17 March 2004

Mice that were transgenic for a T-cell receptor (TCR) specific for ovalbumin peptide323-339 (DO11.10) were able to survive an infection with Mycobacterium tuberculosis for approximately 80 days. This limited early control of infection was associated with gamma interferon production, inducible nitric oxide synthase expression within the lung, and an influx of clonotypic lymphocytes. The control of M. tuberculosis was lost in DO11.10 mice bred in a rag mutant background, demonstrating that the immune responsiveness was recombinase dependent and likely to be associated with the expression of an alternative {alpha} TCR by DO11.10 mice. A characterization of the antigen specificity in DO11.10 TCR transgenic mice demonstrated that the specificity was limited and dominated by the 26-kDa (Rv1411c) lipoprotein of M. tuberculosis. This study identifies this lipoprotein as an important and potent inducer of protective T cells within the lungs of mice infected with M. tuberculosis and therefore as a possible target for vaccination.

* Corresponding author. Present address: Department of Internal Medicine, Center for Microbial Interface Biology, The Ohio State University, Tzagournis MRF Room 214A, 420 West 12th Ave., Columbus, OH 43210. Phone: (614) 292-6724. Fax: (614) 292-9616. E-mail: turner-11{at}medctr.osu.edu.

Editor: A. D. O'Brien

Infection and Immunity, July 2004, p. 3759-3768, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3759-3768.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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