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Infection and Immunity, October 2009, p. 4621-4630, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00415-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cytotoxicity and Secretion of Gamma Interferon Are Carried Out by Distinct CD8 T Cells during Mycobacterium tuberculosis Infection {triangledown} ,{dagger}

Thorbjorg Einarsdottir, Euan Lockhart, and JoAnne L. Flynn*

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

Received 14 April 2009/ Returned for modification 6 July 2009/ Accepted 23 July 2009

The host immune response is generally sufficient to contain Mycobacterium tuberculosis infection. It does not, however, efficiently prevent subsequent infection with M. tuberculosis or provide sterilizing immunity. While the understanding of the immune response generated against this pathogen is incomplete, improvements have been achieved due to advances in immunological tools. In this study, we analyzed the multifunctional nature of primary and memory CD8 T-cell responses generated during murine M. tuberculosis infection. We generated a recombinant M. tuberculosis strain expressing ovalbumin (OVA) epitopes in order to expand the peptides for the detection of CD8 T cells during M. tuberculosis infection and enable us to use OVA-specific reagents. Our results indicate that the majority of M. tuberculosis-specific CD8 T cells are limited to either cytotoxicity or the secretion of gamma interferon (IFN-{gamma}), with cytotoxicity being far more prevalent than IFN-{gamma} secretion. Memory CD8 T cells responded earlier and reached higher levels in the lungs than naïve CD8 T cells, as was expected. They were, however, less cytotoxic and secreted less IFN-{gamma} than newly primed CD8 T cells, suggesting that one factor contributing to bacterial persistence and lack of sterilizing immunity may be the low quality of memory cells that are generated.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, W1144 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261. Phone: (412) 624-7743. Fax: (412) 648-3394. E-mail: joanne{at}pitt.edu

{triangledown} Published ahead of print on 10 August 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: R. P. Morrison

Infection and Immunity, October 2009, p. 4621-4630, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00415-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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