Transgenic expression of IFN-gamma in the murine lens results in multiple ocular abnormalities and an early but self-limited inflammatory response.
The anterior chamber of the eye is known to be an immune privileged site, due to both local and systemic effects on the immune response. Injection of IFN-gamma into the anterior chamber (AC) overcomes the suppression of antigen-specific delayed hypersensitivity responses normally seen in the eye. Transgenic mice expressing increased IFN-gamma in the lens under the alpha A-crystallin promoter were produced to determine whether the proinflammatory effects of IFN-gamma would abolish immune privilege and promote loss of tolerance as has been seen in non-immune privileged tissues. Two alpha C/IFN-gamma transgenic lines are described which demonstrate multiple ocular and lenticular abnormalities some of which are developmental in origin and others that may be secondary to the inflammatory effects of IFN-gamma. A significant inflammatory cell infiltrate which is observed in the AC and vitreous from birth to 4 weeks of age, consists initially of macrophage and polymorphonuclear leukocytes and then CD4+ T lymphocytes. However, the infiltrate is essentially resolved by 6 weeks of age. Therefore, although lens-specific expression of IFN-gamma results in early loss of immune privilege, chronic uveitis does not occur probably due to the lack of continued IFN-gamma expression.
Egan
R M
RM
Department of Microbiology, Albert B. Chandler Medical Center, University of Kentucky, Lexington 40536-0084, USA.
Martin
W D
WD
Stevens
J L
JL
Woodward
J G
JG
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers; D009877:Endophthalmitis / Q000378:metabolism* / Q000473:pathology; D005124:Eye Abnormalities / Q000378:metabolism* / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007908:Lens, Crystalline / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism*
D000954:Antigens, Surface; D015415:Biomarkers; D007371:Interferon-gamma