SEARCH:   Advanced

Blood, 16 July 2009, Vol. 114, No. 3, pp. 580-588. Prepublished online as a Blood First Edition Paper on May 18, 2009; DOI 10.1182/blood-2009-01-200923. This Article Full Text Full Text (PDF) Supplemental Methods, Table, Figures, and Videos All Versions of this Article: blood-2009-01-200923v1 114/3/580    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 Gollmer, K. Articles by Stein, J. V. PubMed PubMed Citation Articles by Gollmer, K. Articles by Stein, J. V. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway Kathrin Gollmer1, François Asperti-Boursin2,3, Yoshihiko Tanaka4,5, Klaus Okkenhaug6, Bart Vanhaesebroeck7, Jeffrey R. Peterson8, Yoshinori Fukui4,5, Emmanuel Donnadieu2,3, and Jens V. Stein1 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland; 2 Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR 8104), Paris, France; 3 Inserm (U567), Paris, France; 4 Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; 5 Japan Science and Technology, CREST, Tokyo, Japan; 6 Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom; 7 Center for Cell Signaling, Institute of Cancer, Queen Mary University of London, London, United Kingdom; and 8 Department of Basic Sciences, Fox Chase Cancer Center, Philadelphia, PA CD4+ T cells use the chemokine receptor CCR7 to home to and migrate within lymphoid tissue, where T-cell activation takes place. Using primary T-cell receptor (TCR)–transgenic (tg) CD4+ T cells, we explored the effect of CCR7 ligands, in particular CCL21, on T-cell activation. We found that the presence of CCL21 during early time points strongly increased in vitro T-cell proliferation after TCR stimulation, correlating with increased expression of early activation markers. CCL21 costimulation resulted in increased Ras- and Rac-GTP formation and enhanced phosphorylation of Akt, MEK, and ERK but not p38 or JNK. Kinase-dead PI3KD910A/D910A or PI3K-deficient TCR-tg CD4+ T cells showed similar responsiveness to CCL21 costimulation as control CD4+ T cells. Conversely, deficiency in the Rac guanine exchange factor DOCK2 significantly impaired CCL21-mediated costimulation in TCR-tg CD4+ T cells, concomitant with impaired Rac- but not Ras-GTP formation. Using lymph node slices for live monitoring of T-cell behavior and activation, we found that G protein-coupled receptor signaling was required for early CD69 expression but not for Ca2+ signaling. Our data suggest that the presence of CCL21 during early TCR signaling lowers the activation threshold through Ras- and Rac-dependent pathways leading to increased ERK phosphorylation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020