Rheumatoid Arthritis: Fasth AE

Fasth AE, Snir O, Johansson AA, Nordmark B, Rahbar A, Af Klint E, Björkström NK, Ulfgren AK, van Vollenhoven RF, Malmström V, Trollmo C. · Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · Arthritis Res Ther. · Pubmed #17825098 links to  free full text

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.

Fasth AE, Cao D, van Vollenhoven R, Trollmo C, Malmström V. · Rheumatology Unit, Department of Medicine, Karolinska Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden. · Scand J Immunol. · Pubmed #15238090 No free full text.

Abstract: CD4+ T cells lacking the costimulatory molecule CD28 have been described both in elderly individuals and in chronic inflammatory disorders, one being rheumatoid arthritis (RA). We, in this study, provide a comprehensive characterization of cell surface markers on and function of such CD28nullCD4+ T cells, as well as correlations with clinical parameters. We conclude that of all surface markers associated with these cells, only CD57 and CD11b are expressed on the majority of them. This CD28null population occurred in one-third of patients with RA and was independent of clinical characteristics. The population was persistent and expanded in peripheral blood, but was excluded from the joint in most patients. Functionally, CD28nullCD4+ T cells were potent effector memory cells with regard to their proliferation and cytokine-secretion profiles. This capacity correlated with a hitherto unpublished surface phenotype, the cells being uniformly CCR7- and CD43high. Moreover, a new terminally differentiated CD45RA+CCR7- population of CD4+ T cells was identified. We would like to suggest that in the unbalanced immune system of patients with autoimmune disease and chronic infection an expanded CD28nullCD4+ T-cell population able to secrete high levels of cytokines is likely to contribute to disease manifestations.