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

Abstract:

:Interphotoreceptor retinoid-binding protein (IRBP) is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU). 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 uveitogenic epitope (residues 161 - 180), under control of MHC class II promoter. Transgene mRNA was detectable in many tissues. Transgenic protein was undetectable by conventional assays, but was detected in thymic tissue by lymphocyte proliferation assay after induction of the promoter. Transgenic mice challenged with p161 - 180 did not develop EAU and had reduced immunological responses, but remained susceptible to EAU induced by whole IRBP, that contains additional uveitogenic epitopes. Disease was also induced by wild type T cells specific to p161 - 180. Thus, extraocular expression of a privileged retinal antigen enhances self tolerance, supporting the notion that sequestration contributes to immune privilege. Exceedingly low levels of transgene expression result in tolerance that is both profound and epitope specific, implying anergy or deletion of the endogenous uveitogenic repertoire. The same level of expression is, however, insufficient to tolerize wild-type effector T cells in the periphery.

journal_name

Eur J Immunol

authors

Xu H,Wawrousek EF,Redmond TM,Nickerson JM,Wiggert B,Chan CC,Caspi RR

doi

10.1002/1521-4141(200001)30:1<272::AID-IMMU272>3.0

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

272-8

issue

1

eissn

0014-2980

issn

1521-4141

pii

10.1002/(SICI)1521-4141(200001)30:01<272::AID-IMMU

journal_volume

30

pub_type

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