Increased frequency of EBV-specific effector memory CD8+ T cells correlates with higher viral load in rheumatoid arthritis.
EBV is a candidate trigger of rheumatoid arthritis (RA). We determined both EBV-specific T cell and B cell responses and cell-associated EBV DNA copies in patients with RA and demographically matched healthy virus carriers. Patients with RA showed increased and broadened IgG responses to lytic and latent EBV-encoded Ags and 7-fold higher levels of EBV copy numbers in circulating blood cells. Additionally, patients with RA exhibited substantial expansions of CD8(+) T cells specific for pooled EBV Ags expressed during both B cell transformation and productive viral replication and the frequency of CD8(+) T cells specific for these Ags correlated with cellular EBV copy numbers. In contrast, CD4(+) T cell responses to EBV and T cell responses to human CMV Ags were unchanged, altogether arguing against a defective control of latent EBV infection in RA. Our data show that the regulation of EBV infection is perturbed in RA and suggest that increased EBV-specific effector T cell and Ab responses are driven by an elevated EBV load in RA.
Lünemann
Jan D
JD
Laboratory of Viral Immunobiology, Christopher H. Browne Center for Immunology and Immune Diseases, Rockefeller University, New York, NY 10021, USA.
Frey
Oliver
O
Eidner
Thorsten
T
Baier
Michael
M
Roberts
Susanne
S
Sashihara
Junji
J
Volkmer
Rudolf
R
Cohen
Jeffrey I
JI
Hein
Gert
G
Kamradt
Thomas
T
Münz
Christian
C
D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019562:Viral Load
D018501:Antirheumatic Agents; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; C417029:EBV-encoded nuclear antigen 1