Decreased T cell reactivity to Epstein-Barr virus infected lymphoblastoid cell lines in multiple sclerosis

Abstract

OBJECTIVE: To investigate T cell and antibody immunity to Epstein-Barr virus (EBV) in multiple sclerosis (MS). METHODS: Immunoglobulin G (IgG) immunity to EBV nuclear antigen 1 (EBNA1) and viral capsid antigen was measured by enzyme linked immunosorbent assays, and T cell immunity was assessed using enzyme linked immunospot assays to measure the frequency of peripheral blood mononuclear cells (PBMC) producing interferon gamma in response to autologous EBV infected B cell lymphoblastoid cell lines (LCL) in 34 EBV seropositive healthy subjects and 34 EBV seropositive patients with MS who had not received immunomodulatory therapy in the previous 3 months. RESULTS: Patients with MS had increased levels of anti-EBNA1 IgG but a decreased frequency of LCL specific T cells compared with healthy subjects. Using purified populations of CD4(+) T cells and CD8(+) T cells, we showed that the LCL specific response resides predominantly in the CD8(+) population, with a frequency 5-7-fold higher than in the CD4(+) population. The decreased CD8(+) T cell response to LCL in MS was not caused by decreased HLA class I expression by LCL, and LCL from MS patients could be killed normally by HLA matched EBV specific cytotoxic CD8(+) T cell clones from healthy subjects. Furthermore, the decreased CD8(+) T cell immunity to EBV was not due to a primary defect in the function of CD8(+) T cells because EBV specific cytotoxic CD8(+) T cell lines could be generated normally from the PBMC of patients with MS. CONCLUSION: This quantitative deficiency in CD8(+) T cell immunity to EBV might be responsible for the accumulation of EBV infected B cells in the brains of patients with MS.