Molecular interactions between T cells and fibroblast-like synoviocytes: role of membrane tumor necrosis factor-alpha on cytokine-activated T cells
| Autor: | Chinh N, Tran, Steven K, Lundy, Peter T, White, Judith L, Endres, Christopher D, Motyl, Raj, Gupta, Cailin M, Wilke, Eric A, Shelden, Kevin C, Chung, Andrew G, Urquhart, David A, Fox |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
musculoskeletal diseases
Interleukin-6 Tumor Necrosis Factor-alpha T-Lymphocytes Cell Membrane Interleukin-17 Synovial Membrane Cell Communication Fibroblasts musculoskeletal system Intercellular Adhesion Molecule-1 Lymphocyte Activation Coculture Techniques Lymphocyte Function-Associated Antigen-1 Arthritis Rheumatoid Cell Adhesion Humans Interleukin-2 skin and connective tissue diseases Cells Cultured Regular Articles |
| Zdroj: | The American journal of pathology. 171(5) |
| ISSN: | 0002-9440 |
| Popis: | The mechanism of fibroblast-like synoviocyte (FLS) transformation into an inflammatory phenotype in rheumatoid arthritis (RA) is not fully understood. FLS interactions with invading leukocytes, particularly T cells, are thought to be a critical component of this pathological process. Resting T cells and T cells activated through the T-cell receptor have previously been shown to induce inflammatory cytokine production by FLS. More recently, a distinct population of T cells has been identified in RA synovium that phenotypically resembles cytokine-activated T (Tck) cells. Using time lapse microscopy, the interactions of resting, superantigen-activated, and cytokine-activated T cells with FLS were visualized. Rapid and robust adhesion of Tck and superantigen-activated T cells to FLS was observed that resulted in flattening of the T cells and a crawling movement on the FLS surface. Tck also readily activated FLS to produce interleukin IL-6 and IL-8 in a cell contact-dependent manner that was enhanced by exogenous IL-17. Although LFA-1 and ICAM-1 co-localized at the Tck-FLS synapse, blocking the LFA-1/ICAM-1 interaction did not substantially inhibit Tck effector function. However, antibody blocking of membrane tumor necrosis factor (TNF)-alpha on the Tck surface did inhibit FLS cytokine production, thus illustrating a novel mechanism for involvement of TNF-alpha in cell-cell interactions in RA synovium and for the effectiveness of TNF-alpha blockade in the treatment of RA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|