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, Nitin J. Karandikar

Research output: Contribution to journalArticle

184 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4222-4231
Number of pages10
JournalBlood
Volume103
Issue number11
DOIs
StatePublished - Jun 1 2004

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Crawford, M. P., Yan, S. X., Ortega, S. B., Mehta, R. S., Hewitt, R. E., Price, D. A., Stastny, P., Douek, D. C., Koup, R. A., Racke, M. K., & 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), 4222-4231. https://doi.org/10.1182/blood-2003-11-4025