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  • Title: Induction of costimulation of human CD4 T cells by tumor necrosis factor-related apoptosis-inducing ligand: possible role in T cell activation in systemic lupus erythematosus.
    Author: Tsai HF, Lai JJ, Chou AH, Wang TF, Wu CS, Hsu PN.
    Journal: Arthritis Rheum; 2004 Feb; 50(2):629-39. PubMed ID: 14872508.
    Abstract:
    OBJECTIVE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has recently been shown to induce costimulation of mouse T cells in conjunction with signals from the T cell receptor. This study was undertaken to investigate TRAIL-induced costimulation of human T cells in order to determine the role of TRAIL-induced T cell activation in human systemic lupus erythematosus (SLE). METHODS: An in vitro T cell stimulation system with immobilized anti-CD3 and recombinant TRAIL receptor DR4-Fc proteins was used to activate human T cells purified from healthy individuals and from patients with SLE. The T cells were stimulated in vitro to assay their proliferation response by (3)H-thymidine incorporation, and their cytokine production by enzyme-linked immunosorbent assay. Activation of p38 MAPK after TRAIL stimulation was detected with specific anti-phospho-p38 MAPK monoclonal antibodies in Western blots. RESULTS: Enhanced T cell proliferation and increased interleukin-2 and interferon-gamma (IFNgamma) production were demonstrated in human T cells after stimulation with immobilized DR4-Fc and anti-CD3 in vitro. TRAIL engagement selectively activated human CD4, rather than CD8, T cells and augmented IFNgamma production. Activation of p38 MAPK was detected after TRAIL-induced T cell activation. T cells isolated from patients with SLE demonstrated a stronger response to TRAIL-induced costimulation, in terms of proliferation and increased up-regulation of CD25 after activation, when compared with T cells from healthy subjects. CONCLUSION: TRAIL engagement induces costimulation of human CD4 T cells via a p38 MAPK-dependent pathway. The results suggest that enhanced reactivity of T cells to autoantigens as a result of TRAIL-induced costimulation may play a role in the development of human autoimmune diseases.
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