The CD69 activation pathway in rheumatoid arthritis synovial fluid T cells.

OBJECTIVE: To study the CD69 activation pathway in synovial fluid (SF) T lymphocytes from patients with rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMC) or SF mononuclear cells (SFMC) were used in proliferation assays with anti-CD69, anti-CD28, anti-CD3, phorbol myristate acetate (PMA), and/or recombinant interleukin-2 (IL-2). CD69+, CD69-, and resting SF T cells were also proliferated. CD25 expression and production of IL-2 after CD69 activation were assessed by flow cytometry and in a bioassay with the IL-2-dependent cell line CTLL-2. RESULTS: RA SFMC did not proliferate either in the presence of anti-CD69 monoclonal antibodies alone or with concomitant PMA activation, when compared with paired or control PBMC. Similar low proliferative responses via the CD3 or CD28 pathway with PMA were observed. This defective proliferation of RA SFMC after stimulation through the CD69 molecule was explained in part by a failure to express CD25 and to produce IL-2. SF CD69- T cells and resting SF T cells had higher rates of proliferation through the alternative costimulatory pathway CD28 than did SF CD69+ T cells or freshly isolated SF T cells. CONCLUSION: Freshly isolated SF T cells present a profound state of hyporesponsiveness through the CD69 and CD28 costimulatory pathways. This state appears to be dependent on the activation status of SF T cells, since CD69- and resting SF T cells showed recovery of the ability to proliferate through the CD28 activation pathway.

Bowel inflammation in anterior uveitis and spondyloarthropathy.

OBJECTIVE: To assess the possible involvement of the bowel in the spectrum of anterior uveitis (AU). METHODS: Ileocolonoscopy and histology studies were performed on 27 patients with AU. RESULTS: Patients with AU had a higher incidence of chronic intestinal inflammation (CII) than controls. CII was present in AU regardless of HLA-B27 status, sacroiliitis or NSAID intake, and was more prevalent in uveitis with high recurrence. CONCLUSION: Bowl inflammation ia a component of the spectrum of AU. This finding supports a HIL-B27 independent common pathogenic link between AU and spondyloarthropathy.

Characterization and regulation of CD69 expression on rheumatoid arthritis synovial fluid T cells.

OBJECTIVE: To study CD69+ synovial fluid (SF) T cells and the mechanisms regulating CD69 expression in rheumatoid arthritis (RA). METHODS: One or 2 color flow cytometry was used to determine CD69 and other surface markers. Cultures of SF T cells alone or mixed with autologous SF non-T cells were used for CD69 maintenance assays. RESULTS: SF T cells were enriched in CD69+. These cells were mainly CD3+, CD8+ and CD25-. CD69 was maintained on SF T cells cultured with SF non-T cells but not when the former were cultured alone or in the presence of different supernatants from RA SF T and non-T cells cultures with sustained CD69 expression. Pretreatment of T and non-T cells with anti-CD18 monoclonal antibody inhibited CD69 expression, while paraformaldehyde-"fixed" non-T cells effectively maintained it. CONCLUSION: SF T cells exhibit a phenotype with evidence of past and recent activation. Our studies demonstrate that most of the recently activated SF T cells are CD8+. We also found that continuous cell-to-cell interaction between T and non-T cells are responsible for the maintenance of this particular state of activation of SF T cells.

CD23 hyperexpression in rheumatoid arthritis: evidence for a B cell hyperresponsiveness to cognate and noncognate T-cell signals.

We have studied the causes of membrane CD23 (mCD23) hyperexpression in rheumatoid arthritis (RA). Modifying a previously developed in vitro system, we cultured RA and control peripheral blood (PB) mononuclear cells for 18 hr with medium, anti-CD3 monoclonal antibody (mAb), recombinant (r) IL-4, or phorbol myristate acetate (PMA). After T cell depletion by rosetting, mCD23 was assessed by indirect immunofluorescence. RA PB B cells expressed mCD23 in a percentage significantly higher than controls unstimulated (16.7% vs. 6.6%) and after culture with anti-CD3-stimulated T cells (53% vs. 37.2%) or IL-4 (47% vs. 30%), but not after PMA (37.5% vs. 31%). We did not see differences in the percentages of resting B cells between RA and controls. Our results show an intrinsic RA PB B cell hyperesponsiveness to different T cell signals that might be mediated by in vivo priming through surface immunoglobulin.