Fas-Fas Ligand-mediated apoptosis within aqueous during idiopathic acute anterior uveitis

A D Dick, K Siepmann, C Dees, L Duncan, C Broderick, J Liversidge, J V Forrester

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Abstract

PURPOSE. Despite ocular immune privilege, (auto)immune-mediated acute anterior uveitis (AAU) is relatively common. However, although relapses of AAU are usually self-limiting, possible regulatory mechanisms remain undefined in humans. Experimentally, Fas-Ligand (FasL)-mediated apoptosis of Fast inflammatory cells contributes to the immune privilege within the anterior chamber anti provides an explanation for the success of corneal allograft transplantation. Therefore, whether such mechanisms regulate the immune response in AAU was investigated.

METHODS. Aqueous and peripheral blood samples from consecutive patients presenting with idiopathic AAU were obtained with consent. Leukocytic phenotype was analyzed by flow cytometry, and apoptosis was determined by both flow cytometry and TdT-dUTP terminal nick-end labeling analysis. Presence of soluble Fas and Fast was determined by western blot :analysis and enzyme-linked immunosorbent assay and compared with control aqueous from patients undergoing cataract surgery. The ability of the aqueous to induce apoptosis in a. Fas(+) Jurkat cell line was also determined.

RESULTS. During AAU aqueous-infiltrating Fas(+) cells included DD3(+) T cells and granulocytes, whereas FasL(+) cells comprised predominantly of non-CD3(+) T cells. Higher levels of functional soluble Fast were found in aqueous of AAU patients than in normal aqueous, capable of inducing apoptosis in 68.9% +/- 7.6% of Fas(+) lymphoid cells. Compared with peripheral blood, the CD4(+) T cells infiltrate within aqueous showed significantly increased CD69 and CD25(IL-2r) expression. Flow cytometric analysis of aqueous showed that 9.32% +/- 1.2% of infiltrating non-granulocyte CD45(+) cells were apoptotic, confirmed as T cells on subsequent three-color flow cytometric analysis.

CONCLUSIONS. Taken together with published experimental data, the present study provides evidence for FasL-mediated apoptotic cell death contributing to the local immune regulation BE ocular inflammatory disease and provides a mechanism to account for the self-limiting clinical course of AAU.

Original languageEnglish
Pages (from-to)2258-2267
Number of pages10
JournalInvestigative Ophthalmology & Visual Science
Volume40
Publication statusPublished - 1999

Keywords

  • TUMOR-NECROSIS-FACTOR
  • ENDOTOXIN-INDUCED UVEITIS
  • POSITIVE DENDRITIC CELLS
  • IMMUNE-PRIVILEGED SITE
  • BLOOD T-LYMPHOCYTES
  • PERIPHERAL-BLOOD
  • (FASL)-INDUCED APOPTOSIS
  • MOLECULAR-BASIS
  • SOLUBLE FORM
  • TNF-ALPHA

Equipment

Iain Fraser Cytometry Centre

Andrea Holme (Manager), Linda Duncan (Senior Application Scientist), Ailsa Laird (Technician) & Kate Burgoyne (Technician)

Institute of Medical Sciences

Research Facilities: Facility

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