Effector function of resting T cells: Activation of synovial fibroblasts

Citation
Y. Yamamura et al., Effector function of resting T cells: Activation of synovial fibroblasts, J IMMUNOL, 166(4), 2001, pp. 2270-2275
Citations number
20
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
166
Issue
4
Year of publication
2001
Pages
2270 - 2275
Database
ISI
SICI code
0022-1767(20010215)166:4<2270:EFORTC>2.0.ZU;2-R
Abstract
Synovial tissue in rheumatoid arthritis is characterized by infiltration wi th large numbers of T lymphocytes and APCs as well as hyperplasia of synovi al fibroblasts. Current understanding of the pathogenesis of RA includes th e concept Bat synovial fibroblasts, which are essential to cartilage and bo ne 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, eve n in the absence of T cell mitogens, induce activation of synovial fibrobla sts 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 import ant in joint inflammation and joint destruction. Furthermore, increased pro duction 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, Restin g T cells also induced synovial fibroblasts to produce PGE(2), indicating a ctivation of expression of the cyclooxygenase 2 gene. Synergy was observed between the effects of IL-17, a cytokine derived from stimulated T cells th at activates fibroblasts, and resting T lymphocytes. Various subsets of T c ells, CD4(+), CD8(+), CD45RO(+), and CD45RA(+) all had comparable ability t o induce synovial fibroblast activation, These results establish an Ag-inde pendent effector function for resting T cells that is likely to be importan t in inflammatory compartments in which large numbers of T lymphocytes and fibroblasts can come into direct contact with each other.