Purchase this article with an account.
C.A. Deeg, B. Amann, A.J. Raith, B. Kaspers; Long Term Study on Epitope Spreading in Horses With Spontaneous Recurrent Uveitis (ERU) . Invest. Ophthalmol. Vis. Sci. 2005;46(13):975.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the occurrence of epitope spreading in horses with spontaneous recurrent uveitis (ERU) to various IRBP and S–antigen derived peptides. Methods: The T cell response of ten horses with ERU was tested in a 8 weeks interval for 18 to 36 months. If an uveitic attack occurred, additional testing of the immune response was performed. Five eye healthy horses served as controls. Peripheral blood lymphocytes were separated as described. Cells were cultured in triplicates (5x105 per well) in flat–bottom microtiter plates (Nunc, Wiesbaden, Germany) for 5 days in the presence of antigens or peptides. Triplicates were stimulated with 5µg/ml whole S–antigen or S–Ag– or IRBP–derived peptides. Subsequently, cells were labeled with 2 µCi [3H] thymidine (Amersham) per well for 18 hours and harvested on day 6. [3H] thymidine incorporation was measured by ß–scintillation counting. The specificity of autoantibodies was tested to S–antigen, IRBP and whole retinal extracts by Western blots and ELISA. Results: T cell responses showed individual variations between ERU horses. Lymphocytes of control horses did not proliferate to the tested antigens. A change in the T cell reaction pattern was observed prior to or during uveitic attacks in the horses that had a relapse during the study. The autoaggressive reaction to this peptide was only seen during a few weeks and then changed to another epitope. Intra– and intermolecular spreading could be measured. Occasional, the proliferation assay was negative for the tested panel of peptides in uveitic attacks. The change in the immune response pattern could not be demonstrated on B cell level using Western blot and ELISA techniques. Conclusions: Here we demonstrate intra– and intermolecular spreading of autoaggressive T cells in horses with spontaneous recurrent uveitis. The association of the spreading with uveitic attacks points to a crucial role in disease pathogenesis.
This PDF is available to Subscribers Only