T-CELL RESPONSE TO EPSTEIN-BARR-VIRUS TRANSACTIVATORS IN CHRONIC RHEUMATOID-ARTHRITIS

Rheumatoid arthritis is a multistep disorder associated with autoimmun e features of yet unknown etiology. Implication of viruses such as Eps tein-Barr virus (EBV) in rheumatoid arthritis pathogenesis has been su spected on the basis of several indirect observations, but thus far, a direct link between EBV and rheumatoid arthritis has not been provide d. Here we show that a large fraction of T cells infiltrating affected joints from a patient with chronic rheumatoid arthritis recognizes tw o EBV transactivators (BZLF1 and BMLF1) in a major histocompatibility complex-restricted fashion. Responses to these EBV antigens by synovia l lymphocytes from several other chronic rheumatoid arthritis patients were readily detectable. Thus these results suggest a direct contribu tion of EBV to chronic rheumatoid arthritis pathogenesis. They also de monstrate for the first time the occurrence of T cell responses agains t EBV transactivating factors, which might be central in the control o f virus reactivation.