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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4798-4806. Prepublished online as a Blood First Edition Paper on February 23, 2006; DOI 10.1182/blood-2005-09-3581. This Article Full Text (PDF) All Versions of this Article: 2005-09-3581v1 107/12/4798    most recent Alert me when this article is cited Alert me if a correction is posted 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 Bonder, C. S Articles by Kubes, P. Search for Related Content PubMed PubMed Citation Articles by Bonder, C. S Articles by Kubes, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 6, 2005 Accepted February 6, 2006 Use of CD44 by CD4+ Th1 and Th2 lymphocytes to roll and adhere Claudine S Bonder*, Stephen R Clark, M U Norman, Pauline Johnson, and Paul Kubes Immunology Research Group, Dept. Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, AB, Canada; Vascular Biology Laboratory, Dept. of Human Immunology, Hanson Institute and Institute for Medical and Veterinary Science, Adelaide, SA, Australia Immunology Research Group, Dept. Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, AB, Canada Microbiology and Immunology, Univeristy of British Columbia, Vancouver, BC, Canada * Corresponding author; email: claudine.bonder{at}imvs.sa.gov.au. Localization of circulating lymphocytes to a site of inflammation is paramount for the development and maintenance of an immune response. In vitro studies using cell lines have previously demonstrated that rolling and adhesion of lymphocytes on endothelium requires CD44 interactions with hyaluronan (HA). To date, whether CD44 has a role in mediating CD4+ polarized Th1 and Th2 lymphocyte interactions with the endothelium in vivo is yet to be determined. In this study we used intravital microscopy to demonstrate that both Th1 and Th2 lymphocytes use CD44 to roll and adhere to TNF-activated microvasculature. Furthermore, chimeric studies imply that CD44 expression by both the endothelium and lymphocytes is essential for these interactions to occur. HA was also necessary for T cell-endothelial cell interactions in vivo and Th1 and Th2 cells rolled on immobilized HA in vitro via CD44. In vitro, we report that both Th1 and Th2 lymphocytes have increased expression of CD44 and greater binding of fluorescent HA than naive cells. The interactions of Th1 and Th2 cells were entirely dependent upon both P-selectin and CD44 in vivo, but did not appear to be counter ligands in vitro. Taken together, these results suggest that CD44 and HA are key to both Th1 and Th2 lymphocyte interactions with the TNF-activated endothelium and raises the possibility of cooperativity between the P-selectin/PSGL-1 and HA/CD44 pathways for Th1 and Th2 rolling in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Guan, P. S. Nagarkatti, and M. Nagarkatti Role of CD44 in the Differentiation of Th1 and Th2 Cells: CD44-Deficiency Enhances the Development of Th2 Effectors in Response to Sheep RBC and Chicken Ovalbumin J. Immunol., July 1, 2009; 183(1): 172 - 180. [Abstract] [Full Text] [PDF] E. Colon, A. Shytuhina, M. K. Cowman, P. A. Band, K. W. Sanggaard, J. J. Enghild, and H.-G. Wisniewski Transfer of Inter-{alpha}-inhibitor Heavy Chains to Hyaluronan by Surface-linked Hyaluronan-TSG-6 Complexes J. Biol. Chem., January 23, 2009; 284(4): 2320 - 2331. [Abstract] [Full Text] [PDF] B. Ruffell and P. Johnson Hyaluronan Induces Cell Death in Activated T Cells through CD44 J. Immunol., November 15, 2008; 181(10): 7044 - 7054. [Abstract] [Full Text] [PDF] R. Zennadi, A. Chien, K. Xu, M. Batchvarova, and M. J. Telen Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium Blood, October 15, 2008; 112(8): 3474 - 3483. [Abstract] [Full Text] [PDF] B. McDonald, E. F. McAvoy, F. Lam, V. Gill, C. de la Motte, R. C. Savani, and P. Kubes Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids J. Exp. Med., April 14, 2008; 205(4): 915 - 927. [Abstract] [Full Text] [PDF] T. A. Jokela, M. Jauhiainen, S. Auriola, M. Kauhanen, R. Tiihonen, M. I. Tammi, and R. H. Tammi Mannose Inhibits Hyaluronan Synthesis by Down-regulation of the Cellular Pool of UDP-N-acetylhexosamines J. Biol. Chem., March 21, 2008; 283(12): 7666 - 7673. [Abstract] [Full Text] [PDF] S. Katoh, N. Ishii, A. Nobumoto, K. Takeshita, S.-Y. Dai, R. Shinonaga, T. Niki, N. Nishi, A. Tominaga, A. Yamauchi, et al. Galectin-9 Inhibits CD44-Hyaluronan Interaction and Suppresses a Murine Model of Allergic Asthma Am. J. Respir. Crit. Care Med., July 1, 2007; 176(1): 27 - 35. [Abstract] [Full Text] [PDF]

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