Cd28 expression on t cell subsets in vivo and cd28‐mediated t cell response in vitro in patients with rheumatoid arthritis

Abstract

In view of the critical importance of the CD28-CD80 (B7/BB1) costimulatory pathway in antigen-specific T cell activation and clonal expansion, we examined CD28 surface molecule expression in vivo, and T cell receptor/CD3-mediated and B7/BB1-costimulated T cell proliferation in vitro, in rheumatoid arthritis (RA). Two-color immunofluorescence analyses of peripheral blood and synovial fluid-derived T cells, as well as 3H-thymidine incorporation assays, were performed. In the peripheral blood of 31 patients with active, untreated 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 in RA patients (mean 233/microliters, versus 292/microliters in controls), and this decrease was more pronounced in patients with severe disease (mean 172/microliters). CD28 expression on peripheral CD8+ T cells in RA patients, but not in healthy individuals, correlated inversely with T cell activation as assessed by HLA-DR antigen expression. In contrast to the peripheral blood, RA synovial fluid T cells were almost exclusively CD28+, suggesting that migration of CD28+CD8+ T cells to active sites of inflammation may occur. In vitro proliferative responses of peripheral blood T cells to B7/BB1 costimulation in the presence of mitogenic doses of anti-CD3 monoclonal antibody were identical in patients with RA and healthy individuals. Functionally intact CD28+ T cells may contribute to the abnormal immunoregulation and joint inflammation in RA.