Tumor Necrosis Factor Receptor Type I Expression of CD4+ T Cells in Rheumatoid Arthritis Enables Them to Follow Tumor Necrosis Factor Gradients Into the Rheumatoid Synovium
| Autor: | Ulf Wagner, Bernd Biedermann, Christoph Baerwald, Manuela Rossol, Jens Grosche, Sebastian Hagen, Andreas Thiel, Matthias Pierer, Kristin Schubert, Anett Schulz, Undine Meusch, R. Scholz |
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| Rok vydání: | 2013 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.medical_treatment T cell Immunology Arthritis Biology medicine.disease Interleukin 21 Cytokine medicine.anatomical_structure Rheumatology Cell culture medicine T cell migration Cancer research Immunology and Allergy Cytotoxic T cell Pharmacology (medical) Tumor necrosis factor alpha |
| Zdroj: | Arthritis & Rheumatism. 65:1468-1476 |
| ISSN: | 0004-3591 |
| DOI: | 10.1002/art.37927 |
| Popis: | Objective The cytokine tumor necrosis factor (TNF) plays a central role in the pathogenesis of rheumatoid arthritis (RA), but its disease-specific effector mechanisms have not been fully elucidated. This study was undertaken to investigate the role of TNF in T cell accumulation and migration in the synovitic joints of RA patients. Methods Vital tissue sections from rheumatoid synovium were generated using a horizontally oscillating microtome and were coincubated with fluorescence-labeled CD4+ T cells. Migration was detected by fluorescence and confocal microscopy. Migrating T cells were recovered from the tissue and analyzed for phenotype. Chemotaxis of CD4+ T cells from RA patients in response to increasing concentrations of TNF was analyzed in Transwell experiments. Results CD4+ T cells from RA patients migrated into the tissue sections in significantly higher numbers than T cells from healthy controls. Migrating CD4+ T cells differed from nonmigrating ones in their increased expression of TNF receptor type I (TNFRI), which was expressed on a fraction of circulating CD4+ T cells from RA patients, but not from controls. CD4+ T cells from the peripheral blood of RA patients were also found to migrate along TNF concentration gradients ex vivo. Accordingly, blockade of either TNF or TNFRI nearly abrogated in vitro T cell migration in synovial tissue. Conclusion Our findings indicate that the interaction of TNF with TNFRI is pivotal for T cell migration in synovial tissue in vitro, and thereby suggest a relevant role of the cytokine for in vivo T cell trafficking to synovitic joints. |
| Databáze: | OpenAIRE |
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