We recently evidenced a dramatic enrichment for T cells reactive against Epstein-Barr virus (EBV) within inflamed joints of two rheumatoid arthritis patients. To assess the generality of this phenomenon and its relevance to autoimmunity, we studied the responses of CD8 T cells from patients with either acute or chronic inflammatory diseases (rheumatoid arthritis: n = 18, ankylosing spondylitis: n = 5, psoriatic arthritis: n = 4, Reiter's syndrome: n = 3, arthrosis: n = 2, uveitis: n = 2, multiple sclerosis: n = 2, encephalitis: n = 1) against viral proteins derived from EBV and another common herpes virus, human cytomegalovirus (CMV). T cell responses against EBV and/or CMV epitopes were frequently observed within CD8 T cells derived from chronic inflammatory lesions, irrespective of their location (knee, eye, brain) and autoimmune features. In most cases, CD8 T cells derived from affected organs yielded stronger anti-viral T cell responses than CD8 T cells derived from patients' PBL, even in chronic inflammatory diseases devoid of autoimmune features or induced by defined bacterial agents. Taken together, these results suggest that the presence of virus-specific T cells within inflamed lesions of patients suffering from autoimmune diseases is a general phenomenon associated with chronic inflammation rather than the initiating cause of the autoimmune process. Since this phenomenon was sometimes associated with long-term T repertoire biases within inflamed lesions, the physiopathological significance of T cell clonal expansions found in a recurrent fashion within chronically inflamed autoimmune lesions should be interpreted with caution.