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

• Published in: BMC neurology Vol. 11; no. 1; p. 95
• Main Authors: Pender, Michael P, Csurhes, Peter A, Pfluger, Casey M M, Burrows, Scott R
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.08.2011; BioMed Central; BMC
• Subjects: Adult; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Separation; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - metabolism; Female; Flow Cytometry; Herpesvirus 4, Human - immunology; Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class II - biosynthesis; Histocompatibility Antigens Class II - immunology; Humans; Male; Middle Aged; Monocytes - immunology; Monocytes - metabolism; Multiple Sclerosis - immunology; Multiple Sclerosis - metabolism; Multiple Sclerosis - virology
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/1471-2377-11-95

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. 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. 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. 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.