Molecular interactions between T cells and fibroblast-like synoviocytes: role of membrane tumor necrosis factor-alpha on cytokine-activated T cells.
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.
Tran
Chinh N
CN
Department of Internal Medicine, Division of Rheumatology, Rheumatic Disease Core Center, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Lundy
Steven K
SK
White
Peter T
PT
Endres
Judith L
JL
Motyl
Christopher D
CD
Gupta
Raj
R
Wilke
Cailin M
CM
Shelden
Eric A
EA
Chung
Kevin C
KC
Urquhart
Andrew G
AG
Fox
David A
DA
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*