Journal article
High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay
Blood, Vol.103(11), pp.4222-4231
06/01/2004
DOI: 10.1182/blood-2003-11-4025
PMID: 14976054
Abstract
AbstractMultiple 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)
Details
- Title: Subtitle
- High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay
- Creators
- Michael P Crawford - 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, MDShirley X Yan - 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, MDSterling B Ortega - 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, MDRiyaz S Mehta - 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, MDRachel E Hewitt - 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, MDDavid A Price - 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, MDPeter Stastny - 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, MDDaniel C Douek - 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, MDRichard A Koup - 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, MDMichael K Racke - 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, MDNitin 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
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.103(11), pp.4222-4231
- DOI
- 10.1182/blood-2003-11-4025
- PMID
- 14976054
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 06/01/2004
- Academic Unit
- Pathology
- Record Identifier
- 9984047796902771
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