Endogenous systemic IFN-gamma has a protective role against ocular autoimmunity in mice.
Locally produced IFN-gamma has been implicated in enhancing inflammation 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 protein (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 increase in the proportion of macrophage/monocytes vs lymphocytes in the ocular lesions of treated animals. The anti-IFN-gamma treatment did not prevent 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 significantly affected by either treatment. Experiments in several genetically resistant strains of mice showed that treatment with anti-IFN-gamma was able to up-regulate disease expression also in some EAU-resistant strains. In the case of one such strain, resistance to EAU induction was completely abrogated by the treatment. We conclude that endogenously 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.
Caspi
R R
RR
National Eye Institute, Bethesda, MD 20892.
Chan
C C
CC
Grubbs
B G
BG
Silver
P B
PB
Wiggert
B
B
Parsa
C F
CF
Bahmanyar
S
S
Billiau
A
A
Heremans
H
H
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D005136:Eye Proteins; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000276:immunology; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins / Q000276:immunology; D014605:Uveitis / Q000276:immunology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial