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 language | English |
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Pages (from-to) | 4222-4231 |
Number of pages | 10 |
Journal | Blood |
Volume | 103 |
Issue number | 11 |
DOIs | |
State | Published - 1 Jun 2004 |