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Human Tenon’s Fibroblast-Produced IFNß and the Prevention of T-Cell Apoptosis

¹ From the Wound Healing Research and Glaucoma Units, Institute of Ophthalmology, University College, London and Moorfields Eye Hospital National Health Service Trust, London; and the ² Departments of Clinical Immunology and ³ Primary Care and Population Sciences, Royal Free and University College Medical School, University of London, United Kingdom.

PURPOSE. Fibroblast–T-cell interactions may contribute to the development of chronic inflammation, a risk factor for trabeculectomy failure. This study was undertaken to determine whether normal and growth-arrested human Tenon’s fibroblasts (HTF) can prevent cytokine deprivation–mediated T-cell apoptosis through the secretion of interferon (IFN)ß.

METHODS. HTF were used either untreated or pretreated with mitomycin-C (MMC; 0.1 or 0.4 mg/ml) or 5-fluorouracil (5FU; 25 or 50 mg/ml). IL2-deprived T cells were cocultured with HTF. T-cell viability was measured at specific time points. Human Tenon’s fibroblast–conditioned medium was used either untreated or treated with a neutralizing antibody against IFNß to block its action, after which IL2-deprived T cells were added and T-cell viability was measured. An image analysis system was used to determine the production of IFNß by either untreated or MMC-treated HTF.

RESULTS. T-cell viability was significantly greater when T cells were cocultured with both untreated and growth-arrested HTF than when T cells were cultured alone (day 7, P = 0.0001). Neutralizing the action of IFNß blocked HTF-mediated T-cell rescue from apoptosis. Both untreated and growth-arrested HTF secrete IFNß, and MMC at 0.4 mg/ml appeared to increase IFNß production.

CONCLUSIONS. Cytokine deprivation–mediated T-cell apoptosis can be prevented by the action of IFNß secreted by both normal and growth-arrested HTF, which suggests that growth-arrested HTF can still participate in an aggressive wound-healing reaction by mediating a persistent inflammatory phase. This may partly explain why some trabeculectomies fail in high-risk patients, despite the use of antimetabolites.

This article has been cited by other articles:

				L Chang, D Siriwardena, M R Wilkins, J G Crowston, A N Akbar, and P T Khaw In vivo production of interferon {beta} by human Tenon's fibroblasts; a possible mediator for the development of chronic conjunctival inflammation Br. J. Ophthalmol., June 1, 2002; 86(6): 611 - 615. [Abstract] [Full Text] [PDF]