High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay

Crawford, M. P., Yan, S., Ortega, S. B., Mehta, R. S., Hewitt, R. E., Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Statsny, P., Douek, D. C., Koup, R. A., Racke, M. K. and Karandikar, N. J. 2004. High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay. Blood 103 (11) , pp. 4222-4231. 10.1182/blood-2003-11-4025

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Abstract

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.

Item Type:	Article
Status:	Published
Schools:	Medicine
Publisher:	American Society of Hematology
ISSN:	0006-4971
Date of First Compliant Deposit:	5 May 2016
Date of Acceptance:	5 February 2004
Last Modified:	01 Nov 2022 10:09
URI:	https://orca.cardiff.ac.uk/id/eprint/90462

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