Interactions between T cell plasma membranes and monocytes

Apolipoprotein A-I inhibits the production of interleukin-1β and tumor necrosis factor-α by blocking contact-mediated activation of monocytes by T lymphocytes

“…Based on the premise that T lymphocytes play a pivotal role in the pathogenesis of chronic inflammatory diseases, we demonstrated that direct cell-cell contact with stimulated T lymphocytes is a major stimulus triggering the production of large amounts of TNF-␣ and IL-1␤ in monocytes. [1][2][3] Various stimuli are able to induce T cells to activate monocytes by direct cellular contact: (1) mitogens, for example, a combination of phytohemagglutinin (PHA) and phorbol myristate acetate (PMA), 1,[4][5][6] (2) cross-linking of CD3 by immobilized anti-CD3 monoclonal antibody (mAb) with or without cross-linking of the costimulatory molecule CD28, 7,8 (3) antigen-recognition on antigen-specific T-cell clones, 8 and (4) cytokines. 9 The identity of the ligands on plasma membrane of stimulated T cells that trigger the signaling of monocytemacrophages as well as that of the counter-ligands on monocytes is still elusive.…”

“…1,4,5,[10][11][12][13][14] Membrane-associated TNF-␣ and IL-1 do not play a crucial part in this cellular interaction, contrasting with their significant role in activation processes induced by stimulated T cells in human fibroblasts/ synoviocytes or microvascular endothelial cells. 2,3,15,16 We hypothesized that, in analogy with other homeostatic systems, natural inhibitors are likely to exist that interfere with the lymphocyte/monocyte interaction. Such inhibitory activity should be present in plasma because stimulated T lymphocytes in the bloodstream of normal subjects or patients during inflammation show little evidence of contact-mediated activation of monocytes.…”

How T-lymphocytes are activated and become activators by cell cell interaction

“…Most T-cell types including T-cell clones, freshly isolated T-lymphocytes and T-cell lines, such as HUT-78 cells, induce IL-1 and TNF-a in monocytes [3][4][5][6]. Various stimuli other than phytohaemagglutinin (PHA)/phorbol myristate acetate (PMA) induce T-lymphocytes to activate monocytes by direct cellular contact including: 1) cross-linking of CD3 by immobilised anti-CD3 monoclonal antibody with or without cross-linking of the co-stimulatory molecule CD28 [9,[16][17][18]; 2) antigen recognition on antigen-specific T-cell clones [9]; and 3) cytokines [19][20][21].…”

“…However, T-cell cytokines such as IL-4, -10, and -13 have predominantly anti-inflammatory effects, and alone, interferon (IFN)-c, IL-2, -15, or -17 display weak activation capacity in terms of IL-1b and TNF-a induction. This has prompted the author9s group to hypothesise and to demonstrate that T-cells exert a pathological effect through direct cellular contact with monocyte-macrophages, inducing massive upregulation of IL-1 and TNF-a [3][4][5][6], such that the production of TNF-a and IL-1b induced in monocytes by membranes isolated from blood-derived stimulated T-lymphocytes or stimulated T-cells (HUT-78) was equivalent to that induced by lipopolysaccharides [1]. Besides triggering proinflammatory cytokine production, contact-mediated activation of monocytes induced the production and/or shedding of cytokine inhibitors such as IL-1-receptor antagonist (IL-1Ra), and soluble receptors of IL-1 and TNF-a [7][8][9].…”

Anti-inflammatory effects of leflunomide on cultured synovial macrophages from patients with rheumatoid arthritis

“…10 In addition, continuing research indicates that A77 1726 seems to down regulate the glycosylation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), inducing a further reduction of the cell-cell contact activation and homing of inflammatory cells during the inflammatory reaction. [15][16][17] Recently, a significantly reduced number of macrophages, a significantly decreased expression of ICAM-1 and vascular cell adhesion molecule-1, and a reduction of TNFα and IL1β was detected in synovial tissue samples obtained from patients with RA after four months of treatment with leflunomide. 18 Because monocytes and macrophages are considered to be the major source of inflammatory mediators in RA synovial tissue, including the inducible cyclo-oxygenase 2 (COX-2), this study aimed at analysing in vitro the possible antiinflammatory effects exerted by A77 1726 on cultured macrophages obtained from the synovial tissue of patients with RA.…”