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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4360-4366. Prepublished online as a Blood First Edition Paper on September 18, 2007; DOI 10.1182/blood-2007-07-104604. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-104604v1 110/13/4360    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Waller, E. C. P. Articles by Wills, M. R. Search for Related Content PubMed PubMed Citation Articles by Waller, E. C. P. Articles by Wills, M. R. Related Collections Immunobiology Cell Cycle Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Differential costimulation through CD137 (4–1BB) restores proliferation of human virus-specific "effector memory" (CD28– CD45RAHI) CD8+ T cells Edward C. P. Waller1, Nicola McKinney1, Ray Hicks1, Andrew J. Carmichael1, J. G. Patrick Sissons1, and Mark R. Wills1 1 Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom In healthy carriers of human cytomegalovirus (HCMV), the virus-specific memory CD8+ T-cell population is often dominated by CD28– CD45RAhi cells that exhibit direct ex vivo cytotoxicity but whose capacity for proliferation and generation of further memory cells has been questioned. We show that when highly purified CD28– CD45RAhi CD8+ T cells are stimulated with viral peptide presented by autologous monocytes, the virus-specific T cells show early up-regulation of CD137 (4–1BB) and CD278 (ICOS), re-express CD28, and proliferate with similarly high cloning efficiency in limiting dilution analysis as CD28+ CD45ROhi cells or CD28– CD45ROhi cells. Using peptide-pulsed autologous fibroblasts transfected with individual costimulatory ligands as antigen presenting cells, we showed CD137L to be a key costimulatory ligand for proliferation of CD28– CD45RAhi CD8+ T cells and not CD80, CD86, or CD275 (ICOSL). Therefore, CD28– CD45RAhi CD8+ T cells were not terminally differentiated but required a specific costimulatory signal for proliferation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. M. Henson, O. Franzese, R. Macaulay, V. Libri, R. I. Azevedo, S. Kiani-Alikhan, F. J. Plunkett, J. E. Masters, S. Jackson, S. J. Griffiths, et al. KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells Blood, June 25, 2009; 113(26): 6619 - 6628. [Abstract] [Full Text] [PDF] R. K. Sharma, K. G. Elpek, E. S. Yolcu, R.-H. Schabowsky, H. Zhao, L. Bandura-Morgan, and H. Shirwan Costimulation as a Platform for the Development of Vaccines: A Peptide-Based Vaccine Containing a Novel Form of 4-1BB Ligand Eradicates Established Tumors Cancer Res., May 15, 2009; 69(10): 4319 - 4326. [Abstract] [Full Text] [PDF] O. C. Goodyear, G. Pratt, A. McLarnon, M. Cook, K. Piper, and P. Moss Differential pattern of CD4+ and CD8+ T-cell immunity to MAGE-A1/A2/A3 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma Blood, October 15, 2008; 112(8): 3362 - 3372. [Abstract] [Full Text] [PDF]

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