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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3212-3220. Prepublished online as a Blood First Edition Paper on December 13, 2005; DOI 10.1182/blood-2005-09-3881. This Article Full Text Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: 2005-09-3881v1 107/8/3212    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 Zimmerman, A. W. Articles by Figdor, C. G. Search for Related Content PubMed PubMed Citation Articles by Zimmerman, A. W. Articles by Figdor, C. G. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Long-term engagement of CD6 and ALCAM is essential for T-cell proliferation induced by dendritic cells Aukje W. Zimmerman, Ben Joosten, Ruurd Torensma, Jane R. Parnes, Frank N. van Leeuwen, and Carl G. Figdor From the Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences (NCMLS), Nijmegen, the Netherlands; and the Department of Internal Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA. Interactions between T cells and antigen-presenting cells (APCs) are the first step in the induction of an adaptive immune response. Here, we show that CD6 and its ligand activated leukocyte cell adhesion molecule (ALCAM) are actively recruited to the antigen-induced dendritic cell (DC)–T-cell contact zone. Moreover, ALCAM-blocking antibodies interfere with DC–T-cell conjugate formation, demonstrating that CD6-ALCAM binding is essential for stable T-cell–APC contact. We now demonstrate that besides their role in establishing initial contacts, CD6-ALCAM interactions are also required during the proliferative phase of the T-cell response; the presence of CD6-blocking antibodies or recombinant ALCAM-Fc proteins results in a strong and sustained inhibition of T-cell proliferation. Furthermore, simultaneous crosslinking of CD6 and CD3 induces enhanced proliferation and transcriptional activity to a similar level as observed after CD3 and CD28 co-crosslinking, demonstrating that CD6 is an important costimulatory molecule. The stability of ALCAM-CD6 binding, which contrasts with transient homotypic ALCAM-ALCAM interactions, further supports the long-lasting effects observed on T-cell proliferation. Taken together, we demonstrate that CD6 and ALCAM form a key adhesive receptor-ligand pair that is not only involved in early DC-T-cell binding but also in sustaining DC-induced T-cell proliferation long after the initial contact has been established. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Ma, L. Visser, H. Roelofsen, M. de Vries, A. Diepstra, G. van Imhoff, T. van der Wal, M. Luinge, G. Alvarez-Llamas, H. Vos, et al. Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes Blood, February 15, 2008; 111(4): 2339 - 2346. [Abstract] [Full Text] [PDF] S.-C. Choi, K. D. Kim, J.-T. Kim, J. W. Kim, H. G. Lee, J.-M. Kim, Y.-S. Jang, D.-Y. Yoon, K. I. Kim, Y. Yang, et al. Expression of human NDRG2 by myeloid dendritic cells inhibits down-regulation of activated leukocyte cell adhesion molecule (ALCAM) and contributes to maintenance of T cell stimulatory activity J. Leukoc. Biol., January 1, 2008; 83(1): 89 - 98. [Abstract] [Full Text] [PDF] J. te Riet, A. W. Zimmerman, A. Cambi, B. Joosten, S. Speller, R. Torensma, F. N. van Leeuwen, C. G. Figdor, and F. de Lange Distinct kinetic and mechanical properties govern ALCAM-mediated interactions as shown by single-molecule force spectroscopy J. Cell Sci., November 15, 2007; 120(22): 3965 - 3976. [Abstract] [Full Text] [PDF] M.-R. Sarrias, M. Farnos, R. Mota, F. Sanchez-Barbero, A. Ibanez, I. Gimferrer, J. Vera, R. Fenutria, C. Casals, J. Yelamos, et al. CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock PNAS, July 10, 2007; 104(28): 11724 - 11729. [Abstract] [Full Text] [PDF] M. A. A. Castro, M. I. Oliveira, R. J. Nunes, S. Fabre, R. Barbosa, A. Peixoto, M. H. Brown, J. R. Parnes, G. Bismuth, A. Moreira, et al. Extracellular Isoforms of CD6 Generated by Alternative Splicing Regulate Targeting of CD6 to the Immunological Synapse J. Immunol., April 1, 2007; 178(7): 4351 - 4361. [Abstract] [Full Text] [PDF] K. Gijzen, P. J. Tacken, A. Zimmerman, B. Joosten, I. J. M. de Vries, C. G. Figdor, and R. Torensma Relevance of DC-SIGN in DC-induced T cell proliferation J. Leukoc. Biol., March 1, 2007; 81(3): 729 - 740. [Abstract] [Full Text] [PDF] N. J. Hassan, S. J. Simmonds, N. G. Clarkson, S. Hanrahan, M. J. Puklavec, M. Bomb, A. N. Barclay, and M. H. Brown CD6 Regulates T-Cell Responses through Activation-Dependent Recruitment of the Positive Regulator SLP-76. Mol. Cell. Biol., September 1, 2006; 26(17): 6727 - 6738. [Abstract] [Full Text] [PDF] Y. Kato, Y. Tanaka, M. Hayashi, K. Okawa, and N. Minato Involvement of CD166 in the Activation of Human {gamma}{delta}T Cells by Tumor Cells Sensitized with Nonpeptide Antigens J. Immunol., July 15, 2006; 177(2): 877 - 884. [Abstract] [Full Text] [PDF] A. Ibanez, M.-R. Sarrias, M. Farnos, I. Gimferrer, C. Serra-Pages, J. Vives, and F. Lozano Mitogen-Activated Protein Kinase Pathway Activation by the CD6 Lymphocyte Surface Receptor J. Immunol., July 15, 2006; 177(2): 1152 - 1159. [Abstract] [Full Text] [PDF]

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