Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis

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Serval ID
serval:BIB_AF138C282868
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis
Journal
Brain
Author(s)
Jilek S., Schluep M., Meylan P., Vingerhoets F., Guignard L., Monney A., Kleeberg J., Le Goff G., Pantaleo G., Du Pasquier R.A.
ISSN
1460-2156
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
131
Number
Pt 7
Pages
1712-1721
Language
english
Abstract
Epstein-Barr virus (EBV) has been associated with multiple sclerosis (MS), however, most studies examining the relationship between the virus and the disease have been based on serologies, and if EBV is linked to MS, CD8+ T cells are likely to be involved as they are important both in MS pathogenesis and in controlling viruses. We hypothesized that valuable information on the link between MS and EBV would be ascertained from the study of frequency and activation levels of EBV-specific CD8+ T cells in different categories of MS patients and control subjects. We investigated EBV-specific cellular immune responses using proliferation and enzyme linked immunospot assays, and humoral immune responses by analysis of anti-EBV antibodies, in a cohort of 164 subjects, including 108 patients with different stages of MS, 35 with other neurological diseases and 21 healthy control subjects. Additionally, the cohort were all tested against cytomegalovirus (CMV), another neurotropic herpes virus not convincingly associated with MS, nor thought to be deleterious to the disease. We corrected all data for age using linear regression analysis over the total cohorts of EBV- and CMV-infected subjects. In the whole cohort, the rate of EBV and CMV infections were 99% and 51%, respectively. The frequency of IFN-gamma secreting EBV-specific CD8+ T cells in patients with clinically isolated syndrome (CIS) was significantly higher than that found in patients with relapsing-remitting MS (RR-MS), secondary-progressive MS, primary-progressive MS, patients with other neurological diseases and healthy controls. The shorter the interval between MS onset and our assays, the more intense was the EBV-specific CD8+ T-cell response. Confirming the above results, we found that EBV-specific CD8+ T-cell responses decreased in 12/13 patients with CIS followed prospectively for 1.0 +/- 0.2 years. In contrast, there was no difference between categories for EBV-specific CD4+ T cell, or for CMV-specific CD4+ and CD8+ T-cell responses. Anti-EBV-encoded nuclear antigen-1 (EBNA-1)-specific antibodies correlated with EBV-specific CD8+ T cells in patients with CIS and RR-MS. However, whereas EBV-specific CD8+ T cells were increased the most in early MS, EBNA-1-specific antibodies were increased in early as well as in progressive forms of MS. Our data show high levels of CD8+ T-cell activation against EBV--but not CMV--early in the course of MS, which support the hypothesis that EBV might be associated with the onset of this disease.
Keywords
Adult, Aged, Antibodies, Viral, CD8-Positive T-Lymphocytes, Cells, Cultured, Cytomegalovirus Infections, Epitopes, T-Lymphocyte, Epstein-Barr Virus Infections, Epstein-Barr Virus Nuclear Antigens, Herpesvirus 4, Human, Humans, Immunity, Cellular, Interferon-gamma, Lymphocyte Activation, Middle Aged, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting
Pubmed
Web of science
Open Access
Yes
Create date
22/01/2009 13:51
Last modification date
25/09/2019 7:10
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