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

Abstract

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.

Circulating cytotoxic CD8+ CD28- T cells in ankylosing spondylitis

“…Clonally expanded CD8 + T cells reactive against these viruses are frequently present in chronic inflammatory lesions [34]. In rheumatoid arthritis patients, CMV-seropositivity has been directly correlated with increased levels of CD8 + CD28 - T cells [20].…”

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Multiorgan Antiviral T Cell Response

“…Patients with viral reactivation of HHV-6 or EBV at day 0 (n = 14, patients 1, 2, 6, 10, 12, 13,17,19,21,22,23,30,31, and 38) more frequently had facial edema (100% versus 70%, P = 0.03), lymphadenopathies (100% versus 58%, P = 0.01), and monocytosis (1740 cells/mm 3 versus 730 cells/mm 3 , P = 0.01) than did patients without (table S1).…”

“…Four hundred and nine sequences from 19 CD8 + T lymphocyte expansions were obtained from 10 patients selected according to the main culprit drugs. Comparison of these nucleic acid sequences with those available in databases or published in the literature (15)(16)(17)(18)(19)(20)(21)(22) showed that 17 of the 19 populations of expanded CD8 + T lymphocyte contained cells with BV CDR3 sequences homologous to EBV-specific TCRs (table S4B). On average, 47% (range, 10 to 90%) of the sequences obtained from CD8 + expanded lymphocytes from DRESS patients had homology with CDR3 regions of EBV-specific CD8 + T lymphocytes (table S4A), suggesting that there is an EBV-driven selection of the CD8 + T lymphocyte response in many patients with DRESS.…”

Immune Aging and Autoimmune Diseases in Children

“…The expansion of CD28-T cell clones in RA patients was accompanied by phenotypic and functional changes, and showed proinflammatory capacities and resistance to apoptosis [53,66]. Abundance of CMV-and EBV-specific DNA in synovial tissue of RA patients has reinforced the notion of a contribution of these latent herpes viruses to autoimmune arthritis and chronic inflammation [67][68][69].…”