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.
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.
Scotet
E
E
INSERM U463, Institut de Biologie, Nantes, France.
Peyrat
M A
MA
Saulquin
X
X
Retiere
C
C
Couedel
C
C
Davodeau
F
F
Dulphy
N
N
Toubert
A
A
Bignon
J D
JD
Lim
A
A
Vie
H
H
Hallet
M M
MM
Liblau
R
R
Weber
M
M
Berthelot
J M
JM
Houssaint
E
E
Bonneville
M
M
D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D019556:COS Cells; D002908:Chronic Disease; D002999:Clone Cells; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007596:Joints / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013582:Synovial Fluid / Q000276:immunology; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D014764:Viral Proteins