Rr. Caspi et al., ENDOGENOUS SYSTEMIC IFN-GAMMA HAS A PROTECTIVE ROLE AGAINST OCULAR AUTOIMMUNITY IN MICE, The Journal of immunology, 152(2), 1994, pp. 890-899
Locally produced IFN-gamma has been implicated in enhancing inflammati
on and in promoting organ-specific autoimmunity. In the present study,
we investigated the influence of systemically available IFN-gamma on
the expression of experimental autoimmune uveoretinitis (EAU) induced
in mice with the retinal Ag, interphotoreceptor retinoid binding prote
in (IRBP). EAU-susceptible B10.A mice treated with a mAb to IFN-gamma
developed much more severe EAU than did the controls and had increased
delayed hypersensitivity (DH) responses to IRBP. There was an increas
e in the proportion of macrophage/monocytes vs lymphocytes in the ocul
ar lesions of treated animals. The anti-IFN-gamma treatment did not pr
event expression of MHC class II within the ocular tissues. Conversely
, treatment with rIFN-gamma ameliorated EAU expression and lowered DH
responses. This occurred despite widespread induction of MHC class II
Ag in the ocular tissues and other organs. In contrast to EAU and DH,
serum antibody titers and lymphocyte proliferation to IRBP were not si
gnificantly affected by either treatment. Experiments in several genet
ically resistant strains of mice showed that treatment with anti-IFN-g
amma was able to up-regulate disease expression also in some EAU-resis
tant strains. In the case of one such strain, resistance to EAU induct
ion was completely abrogated by the treatment. We conclude that endoge
nously produced IFN-gamma at the systemic level acts to down-regulate
EAU in the mouse and that IFN-gamma-related mechanisms may be involved
in conferring resistance to EAU in some mouse genotypes.