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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this? Submitted November 25, 2003 Accepted February 5, 2004 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 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* Pathology, UT Southwestern Medical Center, Dallas, TX, USA Clinical Medicine, University of Oxford, Oxford, United Kingdom Clinical Medicine, University of Oxford, Oxford, United Kingdom; Vaccine Research Center, NIH/NIAID, Bethesda, MD, USA Medicine, UT Southwestern Medical Center, Dallas, TX, USA Vaccine Research Center, NIH/NIAID, Bethesda, MD, USA Neurology, UT Southwestern Medical Center, Dallas, TX, USA; Immunology, UT Southwestern Medical Center, Dallas, TX, USA Pathology, UT Southwestern Medical Center, Dallas, TX, USA; Neurology, UT Southwestern Medical Center, Dallas, TX, USA * Corresponding author; email: nitin{at}pathology.swmed.edu. Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) with features suggestive of T cell-mediated pathology. The majority of prior reports have focused on CD4+ T cells with the underlying assumption that MS is predominantly a CD4+ Th1-mediated disease. In this report, we utilized 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 MS patients 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 MS patients exhibited a more differentiated Th1 phenotype compared to healthy subjects. Similarly, CNS-specific CD8+ T cell responses from MS patients 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 patients that has been underappreciated thus far. The results emphasize the need to evaluate both CD4+ and CD8+ T cell responses in MS and making both subsets a consideration in the development of novel therapeutic strategies. 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. 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