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Infection and Immunity, September 2005, p. 5809-5816, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5809-5816.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Tracking Antigen-Specific CD8 T Lymphocytes in the Lungs of Mice Vaccinated with the Mtb72F Polyprotein

Scott M. Irwin,1* Angelo A. Izzo,1 Steven W. Dow,1 Y. A. W. Skeiky,2 Steven G. Reed,3 Mark R. Alderson,4 and Ian M. Orme1

Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado,1 Aeras Foundation, Bethesda, Maryland,2 Infectious Disease Research Institute, Seattle, Washington,3 Corixa Corporation, Seattle, Washington4

Received 17 November 2004/ Returned for modification 27 January 2005/ Accepted 18 April 2005

This study used a major histocompatibility complex class I tetramer reagent to track antigen-specific CD8 T cells in the lungs of mice immunized with the tuberculosis vaccine candidate Mtb72F. The results show that CD8 T cells recognizing an immunodominant Mtb32-specific epitope could be detected in significant numbers over the course of infection in mice exposed to low-dose aerosol challenge with Mycobacterium tuberculosis and that prior vaccination substantially increased the numbers of these cells early in the lungs. The effector phenotype of the cells was shown by the demonstration that many secreted gamma interferon, but very few contained granzyme B. As the course of the infection progressed, many activated CD8 T cells down-regulated expression of CD45RB and upregulated expression of the interleukin-7 receptor alpha chain, indicating a transition of these cells to a state of memory. These data support the hypothesis that M. tuberculosis-specific CD8 T cells can be targeted by vaccination with the Mtb72F polyprotein.

* Corresponding author. Mailing address: Mycobacterial Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523-1682. Phone: (970) 491-5736. Fax: (970) 491-5125. E-mail: sirwin{at}lamar.colostate.edu.

Editor: J. D. Clements

Infection and Immunity, September 2005, p. 5809-5816, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5809-5816.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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