Defective control of latent Epstein-Barr virus infection in systemic lupus erythematosus.
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.
Kang
Insoo
I
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520, USA.
Quan
Timothy
T
Nolasco
Helena
H
Park
Sung-Hwan
SH
Hong
Myung Sun
MS
Crouch
Jill
J
Pamer
Eric G
EG
Howe
John Greg
JG
Craft
Joe
J
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*
D018984:Epitopes, T-Lymphocyte