Functional and Phenotypical Characterization of Activated T Cells from Intra‐articular Sites in Inflammatory Joint Diseases

Abstract

The presence of activated T lymphocytes bearing interleukin 2 (IL-2) receptors and HLA class II (Ia) antigens accompanied by impaired T cell functions such as a decreased mitogenic responsiveness are characteristic findings, especially in intra-articular sites in chronic inflammatory joint diseases. The objective of the present study was to further characterize these in vivo activated T cells by the investigation of IL-2 production and a possible T cell receptor modulation. IL-2 receptors were found to be expressed primarily in the CD4+ subset. The Ia+ subset expressing both DR and DQ antigens showed a weaker mitogen-induced response as compared to the Ia- fraction. A decreased mitogen-induced IL-2 production and a lower response to anti-CD3 monoclonal antibodies was observed with synovial T lymphocytes as compared to peripheral blood T cells. The density of the CD3 molecule, known to be closely associated with the T cell receptor, was significantly lower in intra-articular sites, while other T cell-specific surface molecules were expressed to a similar extent in both compartments. The decreased synovial T cell mitogenesis was not restored by the addition of lymphokines (IL-1 and IL-2) or blood monocytes, nor by removing CD8+ T cells. These data present further evidence for a significant T cell activation in intra-articular sites in chronic inflammatory joint diseases. The decreased expression of the CD3 glycoprotein suggests a modulation by so far unidentified antigen(s), which could also be responsible for the weak T cell response elicited by polyclonal mitogens.

Self and Nonself Stimulatory Molecules Induce Preferential Expansion of CD5+ B Cells or Activated T Cells of Chagasic Patients, Respectively

“…We have previously shown that circulating activated CD4 þ and CD8 þ T cells are present in high levels in Chagasic patients [3]. Other studies have correlated high levels of T cells expressing HLA-DR with autoimmune pathology [8].…”

“…Moreover, it has been demonstrated that activated CD8 þ T lymphocytes are the major component of the inflammatory infiltrate in human Chagasic cardiac lesions [5]. In other systems, activated T cells as well as CD5 þ B cells have been correlated with auto-immune reactions when these lymphocyte populations were shown to be present in high levels in diseases such as rheumatoid arthritis and lupus erythematosus [6][7][8].…”

The spleen is an important site of T cell activation during human hepatosplenic schistosomiasis

“…The role of CD2+CD3-cells in schistosomiasis is still unclear. Although this cell population presents phenotype indicative of natural killer cells, there are studies demonstrating that CD2+CD3-cells could represent an activated T cell population that lost CD3 marker upon activation (Jahn et al 1987). …”

Treatment of rheumatoid arthritis with an anti‐CD4 monoclonal antibody

“…detectable infectious agents, large numbers of T lymphocytes, including the CD4+ T helperiinducer cell subset, infiltrate the synovium (1,2). Several studies have demonstrated an activated phenotype and altered functional properties of these cells (3,4). Moreover, in animal models, arthritis is inducible in healthy animals solely by the injection of arthritogenic T cell clones or lines (5).…”