Transgenic expression of an immunologically privileged retinal antigen extraocularly enhances self tolerance and abrogates susceptibility to autoimmune uveitis

Citation
H. Xu et al., Transgenic expression of an immunologically privileged retinal antigen extraocularly enhances self tolerance and abrogates susceptibility to autoimmune uveitis, EUR J IMMUN, 30(1), 2000, pp. 272-278
Citations number
28
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
00142980 → ACNP
Volume
30
Issue
1
Year of publication
2000
Pages
272 - 278
Database
ISI
SICI code
0014-2980(200001)30:1<272:TEOAIP>2.0.ZU;2-E
Abstract
Interphotoreceptor retinoid-binding protein (IRBP) is an immunologically pr ivileged retinal antigen that can elicit experimental autoimmune uveitis (E AU). The nature and extent of tolerance to immunologically privileged self antigens is poorly understood. To investigate whether transgenic expression of IRBP extraocularly enhances tolerance and protects from EAU we prepared mice that express half of the mouse IRBP gene, containing a potent uveitog enic epitope (residues 161-180), under control of MHC class II promoter. Tr ansgene mRNA was detectable in many tissues. Transgenic protein was undetec table by conventional assays, but was detected in thymic tissue by lymphocy te proliferation assay after induction of the promoter. Transgenic mice cha llenged with p161-180 did not develop EAU and had reduced immunological res ponses, but remained susceptible to EAU induced by whole IRBP, that contain s additional uveitogenic epitopes. Disease was also induced by wild type T cells specific to p161-180. Thus, extraocular expression of a privileged re tinal antigen enhances self tolerance, supporting the notion that sequestra tion contributes to immune privilege. Exceedingly low levels of transgene e xpression result in tolerance that is both profound and epitope specific, i mplying anergy or deletion of the endogenous uveitogenic repertoire. The sa me level of expression is, however, insufficient to tolerize wild-type effe ctor T cells in the periphery.