Frequent enrichment for CD8 T cells reactive against common herpes virusesin chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes

We recently evidenced a dramatic enrichment for T cells reactive against Ep stein-Barr virus (EBV) within inflamed joints of two rheumatoid arthritis p atients. To assess the generality of this phenomenon and its relevance to a utoimmunity, we studied the responses of CD8 T cells from patients with eit her acute or chronic inflammatory diseases (rheumatoid arthritis: n = 18, a nkylosing spondylitis: n = 5, psoriatic arthritis: n = 4, Reiter's syndrome : n = 3, arthrosis: n = 2, uveitis: n = 2, multiple sclerosis: n = 2, encep halitis: 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 c hronic inflammatory lesions, irrespective of their location (knee, eye, bra in) and autoimmune features. In most cases, CD8 T cells derived from affect ed organs yielded stronger anti-viral T cell responses than CD8 T cells der ived from patients' PBL, even in chronic inflammatory diseases devoid of au toimmune features or induced by defined bacterial agents. Taken together, t hese results suggest that the presence of virus-specific T cells within inf lamed lesions of patients suffering from autoimmune diseases is a general p henomenon associated with chronic inflammation rather than the initiating c ause of the autoimmune process. Since this phenomenon was sometimes associa ted with long-term T repertoire biases within inflamed lesions, the physiop athological significance of T cell clonal expansions found in a recurrent f ashion within chronically inflamed autoimmune lesions should be interpreted with caution.