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Mult Scler. 2016 Mar;22(3):279-91. doi: 10.1177/1352458515588581. Epub 2015 Jun 3.

Intrathecal CD8 T-cells of multiple sclerosis patients recognize lytic Epstein-Barr virus proteins.

Author information

1
Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands/Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
2
Helmholtz Zentrum München and Technical University, Munich, Germany.
3
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands/Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany.
4
Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands.
5
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands/Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany g.verjans@erasmusmc.nl.

Abstract

BACKGROUND:

The association between Epstein-Barr virus (EBV) and multiple sclerosis (MS) may involve intrathecal EBV-specific T-cell responses targeting the virus or indirectly, autoantigens.

OBJECTIVE:

Compare the prevalence and fine-specificity of EBV-specific T-cells in the cerebrospinal fluid (CSF) of patients with MS (n = 12), clinically-isolated syndrome (CIS) (n = 17) and other neurological diseases (OND) (n = 13).

METHODS:

Intrathecal EBV-specific T-cell reactivity was assayed using CSF-derived T-cell lines (CSF-TCL) and autologous EBV-transformed B-cells (autoBLCL) as antigen-presenting cells (APC). EBV proteins recognized by autoBLCL-specific CD8 T-cells were identified using human leukocyte antigen class I (HLA-I)-negative monkey cells as artificial APC, co-transfected with 59 different EBV genes and the corresponding patient's HLA-I alleles that were involved in autoBLCL T-cell reactivity. Reactivity towards the MS-associated autoantigen αB-crystallin (CRYAB) was determined analogously.

RESULTS:

CSF-TCL from CIS and MS patients had significantly higher frequencies of autoBLCL-reactive CD4 T-cells, compared to the OND patients. CIS patients also had significantly higher autoBLCL-reactive CD8 T cells, which correlated with reactive CD4 T-cell frequencies. AutoBLCL-specific CD8 T-cell responses of four CSF-TCL analyzed in detail were oligoclonal and directed to lytic EBV proteins, but not CRYAB endogenously expressed by autoBLCL.

CONCLUSIONS:

Enhanced intrathecal autoBLCL-specific T-cell reactivity, selectively directed towards lytic EBV proteins in two CSF-TCL, suggested a localized T-cell response to EBV in patients with MS. Our data warrant further characterization of the magnitude and breadth of intrathecal EBV-specific T-cell responses in larger patient cohorts.

KEYWORDS:

Autoantibodies; Epstein-Barr virus; T-cells; cerebrospinal fluid; clinically-isolated syndrome; crystallin; disease control; herpesviridae; intrathecal space; lytic antigen; multiple sclerosis; target antigen

PMID:
26041797
DOI:
10.1177/1352458515588581
[Indexed for MEDLINE]

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