Journal article
Molecular Interactions between T Cells and Fibroblast-Like Synoviocytes: Role of Membrane Tumor Necrosis Factor-α on Cytokine-Activated T Cells
The American journal of pathology, Vol.171(5), pp.1588-1598
11/2007
Handle:
https://hdl.handle.net/2376/104302
PMCID: PMC2043519
PMID: 17823284
Abstract
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)-α on the Tck surface did inhibit FLS cytokine production, thus illustrating a novel mechanism for involvement of TNF-α in cell-cell interactions in RA synovium and for the effectiveness of TNF-α blockade in the treatment of RA.
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Details
- Title
- Molecular Interactions between T Cells and Fibroblast-Like Synoviocytes
- Creators
- Chinh N Tran - From the Department of Internal Medicine, Division of RheumatologySteven K Lundy - From the Department of Internal Medicine, Division of RheumatologyPeter T White - University of Michigan Medical SchoolJudith L Endres - From the Department of Internal Medicine, Division of RheumatologyChristopher D Motyl - From the Department of Internal Medicine, Division of RheumatologyRaj Gupta - From the Department of Internal Medicine, Division of RheumatologyCailin M Wilke - From the Department of Internal Medicine, Division of RheumatologyEric A Shelden - From the Department of Internal Medicine, Division of RheumatologyKevin C Chung - From the Department of Internal Medicine, Division of RheumatologyAndrew G Urquhart - From the Department of Internal Medicine, Division of RheumatologyDavid A Fox - From the Department of Internal Medicine, Division of Rheumatology
- Publication Details
- The American journal of pathology, Vol.171(5), pp.1588-1598
- Academic Unit
- School of Molecular Biosciences
- Publisher
- American Society for Investigative Pathology
- Identifiers
- 99900547094101842
- Language
- English
- Resource Type
- Journal article