help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
A more recent version of this article appeared on November 1, 2007

Published online before print September 6, 2007
This Article
Right arrow Full Text (Rapid PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
ajpath.2007.070004v1
171/5/1588    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tran, C. N.
Right arrow Articles by Fox, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tran, C. N.
Right arrow Articles by Fox, D. A.
Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070004

Accepted for publication July 25, 2007.

Article

Molecular Interactions between T Cells and Fibroblast-Like Synoviocytes. Role of Membrane Tumor Necrosis Factor-{alpha} on Cytokine-Activated T Cells

Chinh N. Tran*, Steven K. Lundy*, Peter T. White*, Judith L. Endres*, Christopher D. Motyl*, Raj Gupta*, Cailin M. Wilke*, Eric A. Shelden{dagger}, Kevin C. Chung{ddagger}, Andrew G. Urquhart{sect}, and David A. Fox*@

From the Department of Internal Medicine, Division of Rheumatology,* Rheumatic Disease Core Center, the Department of Surgery,{ddagger} Section of Plastic Surgery, and the Department of Orthopedic Surgery,{sect} University of Michigan Medical School, Ann Arbor, Michigan; and the School of Molecular Biosciences,{dagger} Washington State University, Pullman, Washington

@ To whom correspondence should be addressed. E-mail: dfox{at}umich.edu.


  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)-{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.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2007 by the American Society for Investigative Pathology.