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


CONCLUSIONS
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.
Pender
M P
MP
University of Queensland, School of Medicine, Royal Brisbane and Women's Hospital, Queensland, Australia. m.hawes@uq.edu.au
Csurhes
P A
PA
Lenarczyk
A
A
Pfluger
C M M
CM
Burrows
S R
SR
D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D002470:Cell Survival; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology*; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000032:analysis; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*
D000914:Antibodies, Viral; D006680:HLA Antigens; D007074:Immunoglobulin G