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

Citation
Ad. Dick et al., Fas-Fas Ligand-mediated apoptosis within aqueous during idiopathic acute anterior uveitis, INV OPHTH V, 40(10), 1999, pp. 2258-2267
Citations number
51
Categorie Soggetti
da verificare
Journal title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
ISSN journal
01460404 → ACNP
Volume
40
Issue
10
Year of publication
1999
Pages
2258 - 2267
Database
ISI
SICI code
0146-0404(199909)40:10<2258:FLAWAD>2.0.ZU;2-W
Abstract
PURPOSE. Despite ocular immune privilege, (auto)immune-mediated acute anter ior uveitis (AAU) is relatively common. However, although relapses of AAU a re usually self-limiting, possible regulatory mechanisms remain undefined i n humans. Experimentally, Fas-Ligand (FasL)-mediated apoptosis of Fast infl ammatory cells contributes to the immune privilege within the anterior cham ber anti provides an explanation for the success of corneal allograft trans plantation. Therefore, whether such mechanisms regulate the immune response in AAU was investigated. METHODS. Aqueous and peripheral blood samples from consecutive patients pre senting with idiopathic AAU were obtained with consent. Leukocytic phenotyp e was analyzed by flow cytometry, and apoptosis was determined by both flow cytometry and TdT-dUTP terminal nick-end labeling analysis. Presence of so luble Fas and Fast was determined by western blot :analysis and enzyme-link ed immunosorbent assay and compared with control aqueous from patients unde rgoing 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 cel ls and granulocytes, whereas FasL(+) cells comprised predominantly of non-C D3(+) T cells. Higher levels of functional soluble Fast were found in aqueo us of AAU patients than in normal aqueous, capable of inducing apoptosis in 68.9% +/- 7.6% of Fas(+) lymphoid cells. Compared with peripheral blood, t he 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 apo ptotic, confirmed as T cells on subsequent three-color flow cytometric anal ysis. CONCLUSIONS. Taken together with published experimental data, the present s tudy 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.