Skewed distribution of proinflammatory CD4+CD28null T cells in rheumatoid arthritis.
Expanded populations of CD4+ T cells lacking the co-stimulatory molecule CD28 (CD4+CD28null T cells) have been reported in several inflammatory disorders. In rheumatoid arthritis, increased frequencies of CD4+CD28null T cells in peripheral blood have previously been associated with extra-articular manifestations and human cytomegalovirus (HCMV) infection, but their presence in and contribution to joint manifestations is not clear. In the present article we investigated the distribution of CD4+CD28null T cells in the synovial membrane, synovial fluid and peripheral blood of RA patients, and analysed the association with erosive disease and anti-citrullinated protein antibodies. CD4+CD28null T cells were infrequent in the synovial membrane and synovial fluid, despite significant frequencies in the circulation. Strikingly, the dominant TCR-Vbeta subsets of CD4+CD28null T cells in peripheral blood were often absent in synovial fluid. CD4+CD28null T cells in blood and synovial fluid showed specificity for HCMV antigens, and their presence was clearly associated with HCMV seropositivity but not with anti-citrullinated protein antibodies in the serum or synovial fluid, nor with erosive disease. Together these data imply a primary role for CD4+CD28null T cells in manifestations elsewhere than in the joints of patients with HCMV-seropositive rheumatoid arthritis.
Fasth
Andreas E R
AE
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. andreas.fasth@ki.se
Snir
Omri
O
Johansson
Anna A T
AA
Nordmark
Birgitta
B
Rahbar
Afsar
A
Af Klint
Erik
E
Björkström
Niklas K
NK
Ulfgren
Ann-Kristin
AK
van Vollenhoven
Ronald F
RF
Malmström
Vivianne
V
Trollmo
Christina
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology; D018106:CD28 Antigens / Q000032:analysis / Q000097:blood*; D015704:CD4 Antigens / Q000032:analysis / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008215:Lymphocytes, Null / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D013583:Synovial Membrane / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*