https://scholars.lib.ntu.edu.tw/handle/123456789/545349
標題: | 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 | 作者: | Tsai H.-F. Lai J.-J. Chou A.-H. Wang T.-F. Wu C.-S. PING-NING HSU |
公開日期: | 2004 | 卷: | 50 | 期: | 2 | 起(迄)頁: | 629-639 | 來源出版物: | Arthritis and Rheumatism | 摘要: | 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 3H-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-γ (IFN-γ) 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 IFN-γ 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-1042290323&doi=10.1002%2fart.20038&partnerID=40&md5=a57942da49813668877019f1a43fcb13 https://scholars.lib.ntu.edu.tw/handle/123456789/545349 |
ISSN: | 0004-3591 | DOI: | 10.1002/art.20038 | SDG/關鍵字: | CD4 antigen; CD8 antigen; Dr4 Fc protein; gamma interferon; interleukin 2; interleukin 2 receptor; mitogen activated protein kinase; monoclonal antibody CD3; protein; synaptophysin; T lymphocyte receptor; thymidine derivative; tritium; tumor necrosis factor related apoptosis inducing ligand; unclassified drug; adult; apoptosis; article; autoimmune disease; cell proliferation; clinical article; cytokine production; enzyme linked immunosorbent assay; female; human; interferon production; lymphocyte activation; lymphocyte proliferation; male; pathogenesis; priority journal; protein function; systemic lupus erythematosus; T lymphocyte; Adult; Antibodies, Blocking; Antigens, CD3; Apoptosis Regulatory Proteins; CD4-Positive T-Lymphocytes; Cell Division; Cells, Cultured; Dose-Response Relationship, Drug; Female; Humans; Immunoglobulin Fc Fragments; Immunotoxins; Interferon Type II; Interleukin-2; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Membrane Glycoproteins; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Receptors, Interleukin-2; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha; Up-Regulation |
顯示於: | 醫學系 |
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