Effector function of resting T cells: activation of synovial fibroblasts.

Abstract

Synovial tissue in rheumatoid arthritis is characterized by infiltration with large numbers of T lymphocytes and APCs as well as hyperplasia of synovial fibroblasts. Current understanding of the pathogenesis of RA includes the concept that synovial fibroblasts, which are essential to cartilage and bone destruction, are regulated by cytokines derived primarily from monocyte-macrophage cells. Recently it has been found that synovial fibroblasts can also function as accessory cells for T cell activation by superantigens and other stimuli. We have now found that highly purified resting T cells, even in the absence of T cell mitogens, induce activation of synovial fibroblasts when cocultured for 6-24 h. Such activation was evident by induction or augmentation of mRNA for stromelysin, IL-6, and IL-8, gene products important in joint inflammation and joint destruction. Furthermore, increased production of IL-6 and IL-8 was quantitated by intracellular cytokine staining and flow cytometry. This technique, previously used for analysis of T cell function, was readily adaptable for assays of synovial fibroblasts. Resting T cells also induced synovial fibroblasts to produce PGE(2), indicating activation of expression of the cyclooxygenase 2 gene. Synergy was observed between the effects of IL-17, a cytokine derived from stimulated T cells that activates fibroblasts, and resting T lymphocytes. Various subsets of T cells, CD4(+), CD8(+), CD45RO(+), and CD45RA(+) all had comparable ability to induce synovial fibroblast activation. These results establish an Ag-independent effector function for resting T cells that is likely to be important in inflammatory compartments in which large numbers of T lymphocytes and fibroblasts can come into direct contact with each other.

• Authors: Y Yamamura, R Gupta, Y Morita, X He, R Pai, J Endres, A Freiberg, K Chung, D A Fox
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 166 Issue 4 Pg. 2270-5 (Feb 15 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11160281 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Antigens, Differentiation, T-Lymphocyte
• Cytokines
• Interleukin-17
• RNA, Messenger
• Dinoprostone

Topics

• Adjuvants, Immunologic (pharmacology)
• Antigens, Differentiation, T-Lymphocyte (analysis, biosynthesis)
• Arthritis, Rheumatoid (immunology, pathology)
• Cell Communication (immunology)
• Cell Line
• Coculture Techniques
• Cytokines (biosynthesis, genetics)
• Dinoprostone (biosynthesis)
• Fibroblasts (immunology, metabolism)
• Humans
• Immunophenotyping
• Interleukin-17 (pharmacology)
• Interphase (immunology)
• RNA, Messenger (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• Synovial Membrane (cytology, immunology, metabolism, pathology)
• T-Lymphocyte Subsets (cytology, immunology, metabolism, pathology)