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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shen, C.-H. Articles by Chen, J. Search for Related Content PubMed PubMed Citation Articles by Shen, C.-H. Articles by Chen, J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Flu

Loss of IL-7R and IL-15R Expression Is Associated with Disappearance of Memory T Cells in Respiratory Tract following Influenza Infection¹

Ching-Hung Shen^*, Qing Ge^*, Oezcan Talay^*, Herman N. Eisen^*, Adolfo García-Sastre and Jianzhu Chen^2,*

^* Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; and Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029

Following influenza virus infection, memory CD8 T cells are found in both lymphoid and nonlymphoid organs, where they exhibit striking differences in survival. We have assessed persistence, phenotype, and function of memory CD8 T cells expressing the same TCR in the airways, lung parenchyma, and spleen following influenza virus infection in mice. In contrast to memory CD8 T cells in the spleen, those residing in the airways gradually lost expression of IL-7R and IL-15R, did not respond to IL-7 and/or IL-15, and exhibited poor survival both in vivo and in vitro. Following adoptive transfer into the airways, splenic memory CD8 T cells also down-regulated IL-7R and IL-15R expression and failed to undergo homeostatic proliferation. Thus, although cytokines IL-7 and IL-15 play an essential role in memory CD8 T cell homeostasis in lymphoid organs, the levels of IL-7R and IL-15R expression likely set a threshold for the homeostatic regulation of memory CD8 T cells in the airways. These findings provide a molecular explanation for the gradual loss of airway memory CD8 T cells and heterosubtypic immunity following influenza infection.

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 in part by grants from National Institutes of Health (to J.C. and to A.G.-S.), funds from Singapore-Massachusetts Institute of Technology Alliance (to J.C.), and a Cancer Center Core Grant (to T. Jacks).

² Address correspondence and reprint requests to Dr. Jianzhu Chen, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139. E-mail address: jchen{at}mit.edu

³ Abbreviations used in this paper: SIY, SIYRYYGL peptide; dpi, days post-infection; MLN, mediastinal lymph node; FSC, forward scatter; pStat5, phosphorylated Stat5.

This article has been cited by other articles:

				A. Bai, E. Higham, H. N. Eisen, K. D. Wittrup, and J. Chen From the Cover: Rapid tolerization of virus-activated tumor-specific CD8+ T cells in prostate tumors of TRAMP mice PNAS, September 2, 2008; 105(35): 13003 - 13008. [Abstract] [Full Text] [PDF]