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