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Infection and Immunity, August 2009, p. 3355-3363, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00295-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

CD8 T Cells in Old Mice Contribute to the Innate Immune Response to Mycobacterium tuberculosis via Interleukin-12p70-Dependent and Antigen-Independent Production of Gamma Interferon{triangledown}

Bridget Vesosky,1 Erin K. Rottinghaus,1 Craig Davis,1 and Joanne Turner1,2*

Center for Microbial Interface Biology,1 Division of Infectious Disease, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 432102

Received 13 March 2009/ Returned for modification 24 April 2009/ Accepted 14 May 2009

Elderly individuals have increased morbidity and mortality associated with infectious diseases due in part to the progressive age-associated decline in immune function. Despite this, the old mouse model of Mycobacterium tuberculosis infection has revealed a CD8- and gamma interferon (IFN-{gamma})-dependent early resistance to infection. In this study, we investigated the mechanism by which CD8 T cells from old mice contributed to the early immune response to M. tuberculosis. Following a low-dose aerosol infection with M. tuberculosis, CD8 T cells were identified as being a dominant source of IFN-{gamma} expression in the lungs of old mice early after infection, before the typical onset of antigen-specific immunity. In addition, M. tuberculosis-induced IFN-{gamma} production by CD8 T cells isolated from naïve old mice was major histocompatibility complex class I independent but was dependent on interleukin-12p70, confirming an innate role of CD8 T cells during M. tuberculosis infection. Moreover, the ability of CD8 T cells from old mice to produce increased innate IFN-{gamma} levels in response to M. tuberculosis infection was defined as a unique function of CD8 T cells from old mice and not the aged lung environment. Finally, we have identified increased expression of SET as being one possible mechanism by which CD8 T cells from old mice produce enhanced levels of IFN-{gamma}. Additional characterizations of the signaling events that lead to enhanced innate IFN-{gamma} production by CD8 T cells in old mice may lead to novel strategies to further enhance or perpetuate beneficial immune responses in the elderly.

* Corresponding author. Mailing address: The Ohio State University, BRT 1010, 460 West 12th Avenue, Columbus, OH 43210. Phone: (614) 292-6724. Fax: (614) 292-9616. E-mail: joanne.turner{at}osumc.edu

{triangledown} Published ahead of print on 26 May 2009.

Editor: J. L. Flynn

Infection and Immunity, August 2009, p. 3355-3363, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00295-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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