title: Skewed distribution of proinflammatory CD4+CD28null T cells in rheumatoid arthritis.
abstract: 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.
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. andreas.fasth@ki.se
authors.forename: Andreas E R
authors.initials: AE
authors.lastname: Fasth
authors.forename: Omri
authors.initials: O
authors.lastname: Snir
authors.forename: Anna A T
authors.initials: AA
authors.lastname: Johansson
authors.forename: Birgitta
authors.initials: B
authors.lastname: Nordmark
authors.forename: Afsar
authors.initials: A
authors.lastname: Rahbar
authors.forename: Erik
authors.initials: E
authors.lastname: Af Klint
authors.forename: Niklas K
authors.initials: NK
authors.lastname: Björkström
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Ulfgren
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
authors.forename: Christina
authors.initials: C
authors.lastname: Trollmo
mesh_terms: 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*