Resistance of lymphocytes to Fas-mediated apoptosis in Behçet's disease and Vogt-Koyangi-Harada syndrome

Ocul Immunol Inflamm. 2002 Mar;10(1):47-52. doi: 10.1076/ocii.10.1.47.10331.

Abstract

Background: Behçet's disease and Vogt-Koyanagi-Harada (VKH) syndrome are characterized by a severe intraocular inflammation with a long course and recurrent episodes. Activated autoreactive lymphocytes are considered to be responsible for the development of this inflammation. These lymphocytes may also be involved in the perpetuation and recurrence of this inflammation if they do not properly go into apoptosis. To investigate this hypothesis, a study was carried out to evaluate the resistance of lymphocytes to apoptosis in these two uveitis entities.

Methods: Blood samples were obtained from 17 patients with Behçet's disease, 15 patients with VKH syndrome, and 11 healthy individuals. Mononuclear cells were isolated by centrifugation with Ficoll-Paque and cultured in RPMI 1640 with or without phytohemagglutinin (PHA) for 9 h at 37 degrees C in an atmosphere with 5% CO( 2). The obtained cells were incubated with anti-Fas antibody for 8 h at 37 degrees C in an atmosphere with 5% CO(2). The cells were stained with annexin V/propidium iodide and finally subjected to flow cytometry.

Results: A significantly lower percentage of apoptotic lymphocytes after PHA stimulation was noted in Behçet's disease (19.7 +/- 4.1%) and VKH syndrome (20.4 +/- 6.9%) than in controls (26.1 +/- 7.3%). The percentage of apoptotic lymphocytes without PHA stimulation also tended to be lower in the patients with Behçet's disease (12.6%) and with VKH syndrome (12.8%) than in controls (14.6%), although the difference was not significant.

Conclusion: Lymphocytes in patients with either Behçet's disease or VKH syndrome are relatively resistant to apoptosis mediated by anti-Fas antibody. These apoptosis-resistant, or long-lived, lymphocytes may be involved in the chronic and recurrent intraocular inflammation seen in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis* / immunology
  • Behcet Syndrome / immunology
  • Behcet Syndrome / physiopathology*
  • Female
  • Humans
  • Lymphocytes / physiology*
  • Male
  • Middle Aged
  • Uveomeningoencephalitic Syndrome / immunology
  • Uveomeningoencephalitic Syndrome / physiopathology*
  • fas Receptor / physiology*

Substances

  • fas Receptor