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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2968-2977. Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-10-050724. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-050724v1 109/7/2968    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 Mirenda, V. Articles by Marelli-Berg, F. M. Search for Related Content PubMed PubMed Citation Articles by Mirenda, V. Articles by Marelli-Berg, F. M. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Physiologic and aberrant regulation of memory T-cell trafficking by the costimulatory molecule CD28 Vincenzo Mirenda1, Sarah J. Jarmin1, Rachel David1, Julian Dyson1, Diane Scott1, Yan Gu2, Robert I. Lechler1, Klaus Okkenhaug3, and Federica M. Marelli-Berg1 1 Department of Immunology, Division of Medicine, 2 MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London, United Kingdom; 3 Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom Productive T-cell immunity requires both the activation and the migration of specific T cells to the antigenic tissue. The costimulatory molecule CD28 plays an essential role in the initiation of T-cell–mediated immunity. We investigated the possibility that CD28 may also regulate migration of primed T cells to target tissue. In vitro, CD28-mediated signals enhanced T-cell transendothelial migration, integrin clustering, and integrin-mediated migration. In vivo, T cells bearing a mutation in the CD28 cytoplasmic domain, which abrogates PI3K activation, displayed normal clonal expansion but defective localization to antigenic sites following antigenic rechallenge. Importantly, antibody-mediated CD28 stimulation led to unregulated memory T-cell migration to extra-lymphoid tissue, which occurred independently of T-cell receptor (TCR)–derived signals and homing-receptor expression. Finally, we provide evidence that CD28- and CTLA-4–mediated signals exert opposite effects on T-cell trafficking in vivo. These findings highlight a novel physiologic function of CD28 that has crucial implications for the therapeutic manipulation of this and other costimulatory molecules. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: CD28: beyond just T-cell costimulation Xian C. Li and Mohamed H. Sayegh Blood 2007 109: 2668-2669. [Full Text] [PDF] This article has been cited by other articles: F. Garcon, D. T. Patton, J. L. Emery, E. Hirsch, R. Rottapel, T. Sasaki, and K. Okkenhaug CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer Blood, February 1, 2008; 111(3): 1464 - 1471. [Abstract] [Full Text] [PDF] S. Fuse, W. Zhang, and E. J. Usherwood Control of Memory CD8+ T Cell Differentiation by CD80/CD86-CD28 Costimulation and Restoration by IL-2 during the Recall Response J. Immunol., January 15, 2008; 180(2): 1148 - 1157. [Abstract] [Full Text] [PDF]

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