EXPERIMENTAL AUTOIMMUNE ANTERIOR UVEITIS (EAAU) .2. DOSE-DEPENDENT INDUCTION AND ADOPTIVE TRANSFER USING A MELANIN-BOUND ANTIGEN OF THE RETINAL-PIGMENT EPITHELIUM

被引:55
作者
BROEKHUYSE, RM
KUHLMANN, ED
WINKENS, HJ
机构
[1] Institute of Ophthalmology, University of Nijmegen, 6500 HB Nijmegen
关键词
EXPERIMENTAL AUTOIMMUNE ANTERIOR UVEITIS (EAAU); RETINAL PIGMENT EPITHELIUM; MELANIN; MELANO-ANTIGEN; CELLULAR IMMUNITY; ADOPTIVE TRANSFER; PEP-X; TISSUE SPECIFICITY; SPECIES SPECIFICITY; ANTERIOR UVEITIS;
D O I
10.1016/0014-4835(92)90112-6
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Retinal pigment epithelial cell fractions have been investigated for their capacity to induce expeimental uveitis. Cells of the dark (melanotic) and light areas of the bovine RPE have subsequently been extracted by buffer, Triton X-100, sodium dodecyl sulfate (SDS), and treated with various reagents in order to study some characteristics of the antigen. The SDS-insoluble melanotic fraction, consisting of spindle-shaped, mature melanin granules, proved to be the most uveitogenic preparation. Using pertussis toxin as coadjuvant, 1 μg of melanin-protein (3·4 × 106 granules) was able to induce experimental autoimmune anterior uveitis (EAAU) in Lewis rats. The pathogenic activity of the responsible pathogen (PEP-X) was not diminished by SDS, nor eliminated by mildly alkaline SDS or formic acid treatment. However, HCl-deproteinized granules were not uveitogenic. The results show that PEP-X is a highly stable melanoantigen that is probably covalently bound to the granule surface. This is the first time that a melanin-bound antigen has been demonstrated to evoke specific autoaggressive activity. EAAU could adoptively be transferred by sensitized and in vitro stimulated CD4 T-lymphocytes. The evoked inflammation started 3-4 days after injection, was similar to those induced by immunization, and consisted mainly of severe iridocyclitis accompanied by dense flare and cells in the anterior chamber. Choroiditis developed in severe cases of EAAU but no inflammation was detected in the retina, pineal gland or other organs of these rats. EAAU could not be transferred by serum. Immunized PVG rats and guinea-pigs did not develop ocular inflammation. In monkeys a high dose of antigen evoked a very mild EAAU accompanied by choroiditis. In view of its characteristics, EAAU may be a new model for human anterior uveitis. © 1992.
引用
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页码:401 / 411
页数:11
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