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Prepublished online as a Blood First Edition Paper on February 20, 2003; DOI 10.1182/blood-2002-10-3309. This Article Full Text (PDF) Supplemental Video All Versions of this Article: 2002-10-3309v1 101/12/4775    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 Battistini, L. Articles by Constantin, G. Search for Related Content PubMed PubMed Citation Articles by Battistini, L. Articles by Constantin, G. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted October 31, 2002 Accepted January 31, 2003 CD8+ T cells from acute multiple sclerosis patients display selective increase of adhesiveness in brain venules: a critical role for P-selectin glycoprotein ligand-1 Luca Battistini, Laura Piccio, Barbara Rossi, Simona Bach, Simona Galgani, Claudio Gasperini, Linda Ottoboni, Donatella Ciabini, Maria D Caramia, Giorgio Bernardi, Carlo Laudanna, Elio Scarpini, Rodger P McEver, Eugene C Butcher, Giovanna Borsellino, and Gabriela Constantin* Department of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy Department of Pathology, University of Verona, Verona, Italy Neurological Sciences, IRCCS Ospedale Maggiore, Milan, Italy Department of Neurosciences, San Camillo Hospital, Rome, Italy Department of Neurosciences, University of Tor Vergata, Rome, Italy Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Department of Pathology, Stanford University, Stanford, CA, USA * Corresponding author; email: gabriela.constantin{at}univr.it. Multiple Sclerosis (MS) is considered an autoimmune inflammatory disease of the central nervous system. We compared for the first time the adhesiveness of CD4+ and CD8+ lymphocytes from acute, non-treated patients with the relapsing remitting form of the disease (RRMS) and from healthy donors under physiological conditions. We show that in patients with RRMS CD8+, but not CD4+, T cells display increased rolling and arrest in inflamed murine brain venules. Moreover, CD8+, but not CD4+, lymphocytes from MS patients show increased rolling on P-selectin in vitro. Anti-P-selectin glycoprotein ligand-1 (PSGL-1) antibodies dramatically block the recruitment of CD8+ cells from MS patients in brain vessels, suggesting that PSGL-1 represents a novel pharmaceutical target which may be exploited to block the selective entrance of CD8+ cells during early inflammation. VCAM-1, but not PSGL-1, is critical for the adhesion of CD4+ cells from MS patients, highlighting a fundamental dichotomy in the mechanisms governing the recruitment of lymphocyte subsets in RRMS. Importantly, seven-colour FACS analysis together with functional data indicates that a large fraction of CD8+ cells from MS patients display the characteristics of memory effector phenotype. In conclusion, our results show that CD8+, but not CD4+, T cells from patients with RRMS in the acute phase of the disease display increased ability to be recruited in inflamed brain venules. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: New targets for antiadhesion therapy of human multiple sclerosis Paul Kubes and Steven M. Kerfoot Blood 2003 101: 4648-4649. [Full Text] [PDF] This article has been cited by other articles: B. Bahbouhi, L. Berthelot, S. Pettre, L. Michel, S. Wiertlewski, B. Weksler, I.-A. Romero, F. Miller, P.-O. Couraud, S. Brouard, et al. Peripheral blood CD4+ T lymphocytes from multiple sclerosis patients are characterized by higher PSGL-1 expression and transmigration capacity across a human blood-brain barrier-derived endothelial cell line J. Leukoc. Biol., November 1, 2009; 86(5): 1049 - 1063. [Abstract] [Full Text] [PDF] B. Engelhardt Editorial: PSGL-1--the hidden player in T cell trafficking into the brain in multiple sclerosis? J. Leukoc. Biol., November 1, 2009; 86(5): 1023 - 1025. [Full Text] [PDF] C. Coisne, W. Mao, and B. Engelhardt Cutting Edge: Natalizumab Blocks Adhesion but Not Initial Contact of Human T Cells to the Blood-Brain Barrier In Vivo in an Animal Model of Multiple Sclerosis J. Immunol., May 15, 2009; 182(10): 5909 - 5913. [Abstract] [Full Text] [PDF] J. D. Adams, U. Kim, and H. T. Soh Multitarget magnetic activated cell sorter PNAS, November 25, 2008; 105(47): 18165 - 18170. [Abstract] [Full Text] [PDF] M. Gavina, M. Belicchi, B. Rossi, L. Ottoboni, F. Colombo, M. Meregalli, M. Battistelli, L. Forzenigo, P. Biondetti, F. Pisati, et al. VCAM-1 expression on dystrophic muscle vessels has a critical role in the recruitment of human blood-derived CD133+ stem cells after intra-arterial transplantation Blood, October 15, 2006; 108(8): 2857 - 2866. [Abstract] [Full Text] [PDF] S. M. Kerfoot, M. U. Norman, B. M. Lapointe, C. S. Bonder, L. Zbytnuik, and P. Kubes Reevaluation of P-Selectin and {alpha}4 Integrin as Targets for the Treatment of Experimental Autoimmune Encephalomyelitis J. Immunol., May 15, 2006; 176(10): 6225 - 6234. [Abstract] [Full Text] [PDF] M. A. Friese and L. Fugger Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain, August 1, 2005; 128(8): 1747 - 1763. [Abstract] [Full Text] [PDF] B. Engelhardt, B. Kempe, S. Merfeld-Clauss, M. Laschinger, B. Furie, M. K. Wild, and D. Vestweber P-Selectin Glycoprotein Ligand 1 Is Not Required for the Development of Experimental Autoimmune Encephalomyelitis in SJL and C57BL/6 Mice J. Immunol., July 15, 2005; 175(2): 1267 - 1275. [Abstract] [Full Text] [PDF] L. Piccio, B. Rossi, L. Colantonio, R. Grenningloh, A. Gho, L. Ottoboni, J. W. Homeister, E. Scarpini, M. Martinello, C. Laudanna, et al. Efficient Recruitment of Lymphocytes in Inflamed Brain Venules Requires Expression of Cutaneous Lymphocyte Antigen and Fucosyltransferase-VII J. Immunol., May 1, 2005; 174(9): 5805 - 5813. [Abstract] [Full Text] [PDF] S. M. Kerfoot, E. M. Long, M. J. Hickey, G. Andonegui, B. M. Lapointe, R. C. O. Zanardo, C. Bonder, W. G. James, S. M. Robbins, and P. Kubes TLR4 Contributes to Disease-Inducing Mechanisms Resulting in Central Nervous System Autoimmune Disease J. Immunol., December 1, 2004; 173(11): 7070 - 7077. [Abstract] [Full Text] [PDF] M. P. Crawford, S. X. Yan, S. B. Ortega, R. S. Mehta, R. E. Hewitt, D. A. Price, P. Stastny, D. C. Douek, R. A. Koup, M. K. Racke, et al. High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay Blood, June 1, 2004; 103(11): 4222 - 4231. [Abstract] [Full Text] [PDF] D.-A. Laplaud, C. Ruiz, S. Wiertlewski, S. Brouard, L. Berthelot, M. Guillet, B. Melchior, N. Degauque, G. Edan, P. Brachet, et al. Blood T-cell receptor {beta} chain transcriptome in multiple sclerosis. Characterization of the T cells with altered CDR3 length distribution Brain, May 1, 2004; 127(5): 981 - 995. [Abstract] [Full Text] [PDF] M. Moniuszko, C. Brown, R. Pal, E. Tryniszewska, W.-P. Tsai, V. M. Hirsch, and G. Franchini High Frequency of Virus-Specific CD8+ T Cells in the Central Nervous System of Macaques Chronically Infected with Simian Immunodeficiency Virus SIVmac251 J. Virol., November 15, 2003; 77(22): 12346 - 12351. [Abstract] [Full Text] [PDF]

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