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Open Access Research article

Decreased CD8+ T cell response to Epstein-Barr virus infected B cells in multiple sclerosis is not due to decreased HLA class I expression on B cells or monocytes

Michael P Pender12*, Peter A Csurhes13, Casey MM Pfluger13 and Scott R Burrows4*

Author Affiliations

1 The University of Queensland, School of Medicine, Health Sciences Building, Royal Brisbane and Women's Hospital, Queensland 4029, Australia

2 Department of Neurology, Royal Brisbane and Women's Hospital, Queensland 4029, Australia

3 The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Queensland 4029, Australia

4 Cellular Immunology Laboratory, Queensland Institute of Medical Research, 300 Herston Rd., Brisbane 4029, Australia

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BMC Neurology 2011, 11:95  doi:10.1186/1471-2377-11-95

Published: 3 August 2011

Abstract

Background

Patients with multiple sclerosis (MS) have a decreased frequency of CD8+ T cells reactive to their own Epstein-Barr virus (EBV) infected B cells. We have proposed that this might predispose to the development of MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. The decreased CD8+ T cell response to EBV results from a general CD8+ T cell deficiency and also a decreased proportion of EBV-specific T cells within the total CD8+ T cell population. Because decreased HLA class I expression on monocytes and B cells has been reported in MS and could influence the generation and effector function of EBV-specific CD8+ T cells, the present study was undertaken to measure the expression of HLA molecules on B cells and monocytes in patients with MS.

Methods

We used flow cytometry to determine the proportions of T cells, natural killer cells, B cells and monocytes in peripheral blood mononuclear cells (PBMC) and to quantify the expression of HLA molecules on T cells, B cells and monocytes of 59 healthy subjects and 62 patients with MS who had not received corticosteroids or immunomodulatory therapy in the previous 3 months.

Results

The levels of HLA class I and class II molecules expressed on T cells, B cells and monocytes were normal in patients with MS, with the exception of two patients with secondary progressive MS with very low class II expression on B cells. In confirmation of previous studies we also found that the percentage of CD8+ T cells was significantly decreased whereas the percentage of CD4+ T cells and the CD4:CD8 ratio were significantly increased in patients with MS compared to healthy subjects.

Conclusions

The decreased CD8+ T cell response to EBV-infected B cells in MS patients is not due to decreased HLA class I expression on monocytes or B cells. In a small proportion of patients decreased HLA class II expression on B cells might impair the CD8+ T cell response to EBV by reducing CD4+ T cell help.