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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
- Source :
- Arthritis & Rheumatism. 65:1468-1476
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 00043591
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Arthritis & Rheumatism
- Accession number :
- edsair.doi...........3b677b6782da150f72a2ebb09299675f