T cell response to Epstein-Barr virus transactivators in chronic rheumatoid arthritis.
Rheumatoid arthritis is a multistep disorder associated with autoimmune features of yet unknown etiology. Implication of viruses such as Epstein-Barr virus (EBV) in rheumatoid arthritis pathogenesis has been suspected on the basis of several indirect observations, but thus far, a direct link between EBV and rheumatoid arthritis has not been provided. Here we show that a large fraction of T cells infiltrating affected joints from a patient with chronic rheumatoid arthritis recognizes two EBV transactivators (BZLF1 and BMLF1) in a major histocompatibility complex-restricted fashion. Responses to these EBV antigens by synovial lymphocytes from several other chronic rheumatoid arthritis patients were readily detectable. Thus these results suggest a direct contribution of EBV to chronic rheumatoid arthritis pathogenesis. They also demonstrate for the first time the occurrence of T cell responses against EBV transactivating factors, which might be central in the control of virus reactivation.
Scotet
E
E
Institut National de la Santé et de la Recherche Médicale U211, Institut de Biologie, Nantes, France.
David-Ameline
J
J
Peyrat
M A
MA
Moreau-Aubry
A
A
Pinczon
D
D
Lim
A
A
Even
J
J
Semana
G
G
Berthelot
J M
JM
Breathnach
R
R
Bonneville
M
M
Houssaint
E
E
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology*; D019556:COS Cells; D002908:Chronic Disease; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D018604:Epitope Mapping; D004854:Herpesvirus 4, Human / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014764:Viral Proteins / Q000276:immunology*; D014779:Virus Replication
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins