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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4222-4231. Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-11-4025. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-4025v1 103/11/4222    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 Crawford, M. P. Articles by Karandikar, N. J. Search for Related Content PubMed PubMed Citation Articles by Crawford, M. P. Articles by Karandikar, N. J. Related Collections Immunobiology Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay Michael P. Crawford, Shirley X. Yan, Sterling B. Ortega, Riyaz S. Mehta, Rachel E. Hewitt, David A. Price, Peter Stastny, Daniel C. Douek, Richard A. Koup, Michael K. Racke, and Nitin J. Karandikar From the Departments of Pathology, Internal Medicine, and Neurology, University of Texas Southwestern Medical Center, Dallas; Center for Immunology, University of Texas Southwestern Medical Center, Dallas; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; and The Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD. Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) with features suggestive of T-cell-mediated pathology. Most prior reports have focused on CD4+ T cells with the underlying assumption that MS is predominantly a CD4+ T helper 1 (Th1)-mediated disease. In this report, we used a novel flow cytometric approach to evaluate autoreactive T-cell responses against a large variety of neuroantigenic targets. We found that both CD4+ and CD8+ T cells targeted against several CNS autoantigens were widely prevalent in patients with MS and healthy individuals. Whereas the distribution of CD4+ responses was similar in different groups, patients with relapsing-remitting MS showed a higher proportion of CNS-specific CD8+ responses. Autoreactive CD4+ T cells from patients with MS exhibited a more differentiated Th1 phenotype compared with healthy subjects. Similarly, CNS-specific CD8+ T-cell responses from patients with MS were functionally distinct from those in healthy individuals. Collectively, these studies reveal the high prevalence of class I-restricted autoreactive CD8+ T-cell responses in MS that has been underappreciated thus far. The results emphasize the need to evaluate both CD4+ and CD8+ T-cell responses in MS and to make both subsets a consideration in the development of novel therapeutic strategies. (Blood. 2004; 103:4222-4231) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Spotlight on CD8 T cells in MS Caroline C. Whitacre Blood 2004 103: 3999-4000. [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. Sobottka, M. D. Harrer, U. Ziegler, K. Fischer, H. Wiendl, T. Hunig, B. Becher, and N. Goebels Collateral Bystander Damage by Myelin-Directed CD8+ T Cells Causes Axonal Loss Am. J. Pathol., September 1, 2009; 175(3): 1160 - 1166. [Abstract] [Full Text] [PDF] S.-Y. Na, H. Eujen, K. Gobel, S. G. Meuth, K. Martens, H. Wiendl, and T. Hunig Antigen-Specific Blockade of Lethal CD8 T-Cell Mediated Autoimmunity in a Mouse Model of Multiple Sclerosis J. Immunol., May 15, 2009; 182(10): 6569 - 6575. [Abstract] [Full Text] [PDF] J. Wang, Z.-H. Lu, H.-J. Gabius, C. Rohowsky-Kochan, R. W. Ledeen, and G. 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