CD28 EXPRESSION ON T-CELL SUBSETS IN-VIVO AND CD28-MEDIATED T-CELL RESPONSE IN-VITRO IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective. In view of the critical importance of the CD28-CD80 (B7/BB1 ) costimulatory pathway in antigen-specific T cell activation and clon al expansion, we examined CD28 surface molecule expression in vivo, an d T cell receptor/CD3-mediated and B7/BB1-costimulated T cell prolifer ation in vitro, in rheumatoid arthritis (RA), Methods. Two-color immun ofluorescence analyses of peripheral blood and synovial fluid-derived T cells, as well as H-3-thymidine incorporation assays, were performed , Results. In the peripheral blood of 31 patients with active, untreat ed RA, a mean of 91% (range 48-100%) of CD4+ and 46% (range 13-82%) of CD8+ T cell subsets were CD28+ which was not significantly lower than normal, Although an overall decrease in the number of T cells was not observed, the numbers of CD28+CD8+ T cells were significantly lower i n RA patients (mean 233/mu l, versus 292/mu l in controls), and this d ecrease was more pronounced in patients with severe disease (mean 172/ mu l). CD28 expression on peripheral CD8+ T cells in RA patients, but not in healthy individuals, correlated inversely with T cell activatio n as assessed by HLA-DR antigen expression, In contrast to the periphe ral blood, RA synovial fluid T cells were almost exclusively CD28+, su ggesting that migration of CD28+CD8+ T cells to active sites of inflam mation may occur, In vitro proliferative responses of peripheral blood T cells to B7/BB1 costimulation in the presence of mitogenic doses of anti-CDS monoclonal antibody were identical in patients with RA and h ealthy individuals. Conclusion. Functionally intact CD28+ T cells may contribute to the abnormal immunoregulation and joint inflammation in RA.