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CVI Accepts, published online ahead of print on 28 May 2008
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Clin. Vaccine Immunol. doi:10.1128/CVI.00019-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The influence of BCG vaccination on the cellular immune response in immune guinea pigs infected with Mycobacterium tuberculosis

Diane Ordway*, Marcela Henao-Tamayo, Crystal Shanley, Erin E. Smith, Gopinath Palanisamy, Baolin Wang, Randall J. Basaraba, and Ian M. Orme

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

* To whom correspondence should be addressed. Email: D.Ordway-Rodriguez{at}colostate.edu.


   Abstract

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) currently remains the only licensed vaccine for the prevention of tuberculosis. In this study we used a newly described flow cytometric technique to monitor changes in cell populations accumulating in the lungs and lymph nodes of naïve and vaccinated guinea pigs challenged by low dose aerosol infection with virulent Mycobacterium tuberculosis. As anticipated, vaccinated guinea pigs controlled the growth of the challenge infection more efficiently than controls. This early phase of bacterial control in immune animals was associated with increased accumulation of CD4 and CD8 T cells, including cells expressing the activation marker CD45, as well as macrophages expressing Class II MHC molecules. As the infection continued the numbers of T cells in the lungs of vaccinated animals waned whereas the numbers of these cells expressing CD45 increased. Whereas BCG vaccination reduced the influx of heterophils (neutrophils) into the lungs, an early B cell influx was observed in these vaccinated animals. Overall, vaccine protection was associated with reduced pathology and lung damage in the vaccinated animals. These data provide the first direct evidence that BCG vaccination accelerates the influx of protective T cell and macrophage populations into the infected lungs, diminishes the accumulation of non-protective cell populations, and reduces the severity of lung pathology.







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