Research article

Skewed distribution of proinflammatory CD4⁺CD28^null T cells in rheumatoid arthritis

Andreas ER Fasth¹ , Omri Snir¹ , Anna AT Johansson¹ , Birgitta Nordmark¹ , Afsar Rahbar² , Erik af Klint¹ , Niklas K Björkström³ , Ann-Kristin Ulfgren¹ , Ronald F van Vollenhoven¹ , Vivianne Malmström^{* 1} and Christina Trollmo^{* 1}

¹Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

²Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

³Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

author email corresponding author email* Contributed equally

Arthritis Research & Therapy 2007, 9:R87doi:10.1186/ar2286

Published:	7 September 2007

Abstract

Expanded populations of CD4⁺ T cells lacking the co-stimulatory molecule CD28 (CD4⁺CD28^null T cells) have been reported in several inflammatory disorders. In rheumatoid arthritis, increased frequencies of CD4⁺CD28^null 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⁺CD28^null 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⁺CD28^null T cells were infrequent in the synovial membrane and synovial fluid, despite significant frequencies in the circulation. Strikingly, the dominant TCR-Vβ subsets of CD4⁺CD28^null T cells in peripheral blood were often absent in synovial fluid. CD4⁺CD28^null 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⁺CD28^null T cells in manifestations elsewhere than in the joints of patients with HCMV-seropositive rheumatoid arthritis.