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Blood, 3 September 2009, Vol. 114, No. 10, pp. 2121-2130. Prepublished online as a Blood First Edition Paper on July 17, 2009; DOI 10.1182/blood-2009-05-220087. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2009-05-220087v1 114/10/2121    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Allam, A. Articles by Ashwell, J. D. PubMed PubMed Citation Articles by Allam, A. Articles by Ashwell, J. D. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The CD8+ memory T-cell state of readiness is actively maintained and reversible Atef Allam1, Dietrich B. Conze1, Maria Letizia Giardino Torchia1, Ivana Munitic1, Hideo Yagita2, Ryan T. Sowell3, Amanda L. Marzo3, and Jonathan D. Ashwell1 1 Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD; 2 Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; and 3 Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL The ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory T-cell function is an irreversible differentiation event. In this study, we report that many phenotypic and functional characteristics of antigen-specific CD8 memory T cells are lost when they are deprived of contact with dendritic cells. Under these circumstances, memory T cells reverted from G1 to the G0 cell-cycle state and responded to stimulation like naive T cells, as assessed by proliferation, dependence upon costimulation, and interferon- production, without losing cell surface markers associated with memory. The memory state was maintained by signaling via members of the tumor necrosis factor receptor superfamily, CD27 and 4-1BB. Foxo1, a transcription factor involved in T-cell quiescence, was reduced in memory cells, and stimulation of naive CD8 cells via CD27 caused Foxo1 to be phosphorylated and emigrate from the nucleus in a phosphatidylinositol-3 kinase–dependent manner. Consistent with these results, maintenance of G1 in vivo was compromised in antigen-specific memory T cells in vesicular stomatitis virus-infected CD27-deficient mice. Therefore, sustaining the functional phenotype of T memory cells requires active signaling and maintenance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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