HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dudani, R. Articles by Sad, S. Search for Related Content PubMed PubMed Citation Articles by Dudani, R. Articles by Sad, S.

IFN- Induces the Erosion of Preexisting CD8 T Cell Memory during Infection with a Heterologous Intracellular Bacterium¹

Renu Dudani^*, Kaja Murali-Krishna, Lakshmi Krishnan^*, and Subash Sad^2,*,

^* National Research Council-Institute for Biological Sciences, Ottawa, Ontario, Canada; Department of Immunology, University of Washington, Seattle, WA 98195; and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada

Memory T cells are critical for the control of intracellular pathogens and require few signals for maintenance; however, erosion of established preexisting memory CD8⁺ T cells has been shown to occur during infection with heterologous viral infections. We evaluated whether this also occurs during infection with various intracellular bacteria and what mechanisms may be involved. We demonstrate that erosion of established memory is also induced during infection of mice with various intracellular bacteria, such as Listeria monocytogenes, Salmonella typhimurium, and Mycobacterium bovis (bacillus Calmette-Guérin). The extent of erosion of established CD8⁺ T cell memory was dependent on the virulence of the heterologous pathogen, not persistence. Furthermore, when antibiotics were used to comprehensively eliminate the heterologous pathogen, the numbers of memory CD8⁺ T cells were not restored, indicating that erosion of preexisting memory CD8⁺ T cells was irreversible. Irrespective of the initial numbers of memory CD8⁺ T cells, challenge with the heterologous pathogen resulted in a similar extent of erosion of memory CD8⁺ T cells, suggesting that cellular competition was not responsible for erosion. After challenge with the heterologous pathogen, effector memory CD8⁺ T cells were rapidly eliminated. More importantly, erosion of preexisting memory CD8⁺ T cells was abrogated in the absence of IFN-. These studies help reveal the paradoxical role of IFN-. Although IFN- promotes the control of intracellular bacterial replication during primary infection, this comes at the expense of erosion of preexisting memory CD8⁺ T cells in the wake of infection with heterologous pathogens.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Canadian Institutes of Health Research.

² Address correspondence and reprint requests to Dr. Subash Sad, National Research Council Canada, 1200 Montreal Road, Building M-54, Ottawa, Ontario K1A OR6, Canada. E-mail address: subash.sad{at}nrc.ca

³ Abbreviations used in this paper: LM, Listeria monocytogenes; ST, Salmonella typhimurium; BCG, Mycobacterium bovis; BHI, brain-heart infusion; WT, wild type.