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Infection and Immunity, November 2009, p. 4837-4846, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00704-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Kinetics of the Immune Response Profile in Guinea Pigs after Vaccination with Mycobacterium bovis BCG and Infection with Mycobacterium tuberculosis{triangledown}

Ajay Grover, Jennifer Taylor, JoLynn Troudt, Andrew Keyser, Kimberly Arnett, Linda Izzo, Drew Rholl, and Angelo Izzo*

Colorado State University, Department of Microbiology, Immunology, and Pathology, Fort Collins, Colorado 80523

Received 23 June 2009/ Returned for modification 24 August 2009/ Accepted 2 September 2009

The guinea pig model of tuberculosis is used extensively in assessing novel vaccines, since Mycobacterium bovis BCG vaccination effectively prolongs survival after low-dose aerosol infection with virulent M. tuberculosis. To better understand how BCG extends time to death after pulmonary infection with M. tuberculosis, we examined cytokine responses postvaccination and recruitment of activated T cells and cytokine response postinfection. At 10 weeks postvaccination, splenic gamma interferon (IFN-{gamma}) mRNA was significantly elevated compared to the levels at 5 weeks in ex vivo stimulation assays. At 15, 40, 60, and 120 days postinfection, T-cell activation (CD4+ CD62Llow and CD8+ CD62Llow) and mRNA expression of IFN-{gamma}, tumor necrosis factor alpha (TNF-{alpha}), interleukin-1 (IL-1), IL-10, IL-12, and eomesodermin were assessed. Our data show that at day 40, BCG-vaccinated guinea pigs had significantly increased levels of IFN-{gamma} mRNA expression but decreased TNF-{alpha} mRNA expression in their lungs compared to the levels in nonvaccinated animals. At day 120, a time when nonvaccinated guinea pigs succumbed to infection, low levels of IFN-{gamma} mRNA were observed even though there were increasing levels of IL-1, IL-12, and IL-10, and the numbers of activated T cells did not differ from those in BCG-vaccinated animals. BCG vaccination conferred the advantage of recruiting greater numbers of CD4+ CD62Llow T cells at day 40, although the numbers of CD8+ CD62Llow T cells were not elevated compared to the numbers in nonvaccinated animals. Our data suggest that day 40 postinfection may be a pivotal time point in determining vaccine efficacy and prolonged survival and that BCG promotes the capacity of T cells in the lungs to respond to infection.

* Corresponding author. Mailing address: Colorado State University, Department of Microbiology, Immunology, and Pathology, 1682 Campus Delivery, Fort Collins, CO 80523. Phone: (970) 491-4350. Fax: (970) 491-1815. E-mail: Angelo.Izzo{at}colostate.edu

{triangledown} Published ahead of print on 8 September 2009.

Editor: J. L. Flynn

Infection and Immunity, November 2009, p. 4837-4846, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00704-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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