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The Journal of Immunology, 2007, 178: 2737-2745.
Copyright © 2007 by The American Association of Immunologists, Inc.

Virus-Specific CD8+ T Cells in the Liver: Armed and Ready to Kill1

Rachael Keating, Wen Yue, John A. Rutigliano, Jenny So, Elvia Olivas, Paul G. Thomas and Peter C. Doherty2

Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105

Influenza A virus infection of C57BL/6 mice is a well-characterized model for studying CD8+ T cell-mediated immunity. Analysis of primary and secondary responses showed that the liver is highly enriched for CD8+ T cells specific for the immunodominant H2DbNP366–374 (DbNP366) epitope. Functional analysis established that these liver-derived virus-specific CD8+ T cells are fully competent cytotoxic effectors and IFN-{gamma} secretors. In addition, flow cytometric analysis of early apoptotic cells showed that these influenza-specific CD8+ T cells from liver are as viable as those in the spleen, bronchoalveolar lavage, mediastinal lymph nodes, or lung. Moreover, cytokine profiles of the influenza-specific CD8+ T cells recovered from different sites were consistent with the bronchoalveolar lavage, rather than liver population, being the most susceptible to activation-induced cell death. Importantly, adoptively transferred influenza virus-specific CD8+ T cells from the liver survived and were readily recalled after virus challenge. Together, these results show clearly that the liver is not a "graveyard" for influenza virus-specific CD8+ T cells.

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 Grants AI170251 and AI065097 and by ALSAC at St. Jude Children’s Research Hospital. P.C.D. is also a Burnet Fellow of the Australian National Health and Medical Research Council.

2 Address correspondence and reprint requests to Dr. Peter Doherty, Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105. E-mail address: Peter.Doherty{at}stjude.org

3 Abbreviations used in this paper: AICD, activation-induced cell death; LM, Listeria monocytogenes; BAL, bronchoalveolar lavage; i.n., intranasal(ly); EID50, egg 50% infective dose; PR8, A/Puerto Rico/8/34 influenza A virus; MLN, mediastinal lymph node; NP, nucleoprotein; DEX, dexamethasone; PI, propidium iodide.




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