Local production of IFN-gamma abrogates the intraocular immune privilege in transgenic mice and prevents the induction of ACAID.
The eye represents an immunologically privileged site with specific properties mediated by immunosuppressive constituents of the intraocular fluids. This system, termed ACAID (anterior chamber-associated immune deviation), was originally attributed to the anterior chamber of the eye, and is characterized by impairment of the cellular immune response, including a lack of delayed type hypersensitivity (DTH) reaction in response to intraocularly presented Ag and decreased cytotoxicity of T cells. We created a transgenic mouse with ectopic expression of IFN-gamma in the photoreceptors of the retina to study the effects of this cytokine on the immunosuppressive properties of the eye with special regard to the posterior chamber. BALB/c-derived transgenic and nontransgenic mice were challenged intravitreally either with allogeneic splenocytes from C57Bl/6 mice or with BSA, in IFA, and tested for the delayed type hypersensitivity reaction to BSA by intrapinnal injection of the same Ag in the ear 7 days later. Pathologic changes of the eyes were evaluated by histology and immunohistochemistry. We found that transgenic mice developed an increased amount of ocular inflammation in response to both Ags compared with the nontransgenic controls. Furthermore, transgenic mice showed a marked DTH reaction to BSA, whereas nontransgenic mice did not. Our results indicate that local IFN-gamma production disturbs the immunosuppressive properties of the eye and prevents the induction of ACAID in response to intraocularly presented Ag. The data confirm the extension of the intraocular immune privilege to the posterior chamber of the eye.
Geiger
K
K
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Sarvetnick
N
N
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis; D005123:Eye / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012710:Serum Albumin, Bovine / Q000276:immunology; D013154:Spleen / Q000276:immunology; D015854:Up-Regulation
D018122:B7-1 Antigen; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma