title: Defective control of latent Epstein-Barr virus infection in systemic lupus erythematosus.
abstract: EBV infection is more common in patients with systemic lupus erythematosus (SLE) than in control subjects, suggesting that this virus plays an etiologic role in disease and/or that patients with lupus have impaired EBV-specific immune responses. In the current report we assessed immune responsiveness to EBV in patients with SLE and healthy controls, determining virus-specific T cell responses and EBV viral loads using whole blood recall assays, HLA-A2 tetramers, and real-time quantitative PCR. Patients with SLE had an approximately 40-fold increase in EBV viral loads compared with controls, a finding not explained by disease activity or immunosuppressive medications. The frequency of EBV-specific CD69+ CD4+ T cells producing IFN-gamma was higher in patients with SLE than in controls. By contrast, the frequency of EBV-specific CD69+ CD8+ T cells producing IFN-gamma in patients with SLE appeared lower than that in healthy controls, although this difference was not statistically significant. These findings suggest a role for CD4+ T cells in controlling, and a possible defect in CD8+ T cells in regulating, increased viral loads in lupus. These ideas were supported by correlations between viral loads and EBV-specific T cell responses in lupus patients. EBV viral loads were inversely correlated with the frequency of EBV-specific CD69+ CD4+ T cells producing IFN-gamma and were positively correlated with the frequencies of CD69+ CD8+ T cells producing IFN-gamma and with EBV-specific, HLA-A2 tetramer-positive CD8+ T cells. These results demonstrate that patients with SLE have defective control of latent EBV infection that probably stems from altered T cell responses against EBV.
authors.affiliation: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Insoo
authors.initials: I
authors.lastname: Kang
authors.forename: Timothy
authors.initials: T
authors.lastname: Quan
authors.forename: Helena
authors.initials: H
authors.lastname: Nolasco
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Myung Sun
authors.initials: MS
authors.lastname: Hong
authors.forename: Jill
authors.initials: J
authors.lastname: Crouch
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.forename: John Greg
authors.initials: JG
authors.lastname: Howe
authors.forename: Joe
authors.initials: J
authors.lastname: Craft
mesh_terms: D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D019562:Viral Load; D017735:Virus Latency / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte