Immune privilege and suppression of immunogenic inflammation in the anterior chamber of the eye.
Immunologic privilege of the anterior chamber has been associated with the capacity to induce a unique form of deviant systemic immunity after anterior chamber (AC) immunization. However, the capacity of privilege to suppress expression of immunity in the AC has not been examined. We studied the ability of the AC to sustain immunogenic inflammation after direct antigen challenge (delayed hypersensitivity-DH) in C57BL/6 mice primed to M tuberculosis (MT) antigens. Compared to subcutaneous and subconjunctival sites where primed mice demonstrated vigorous and significant DH, the anterior chambers of these mice failed to develop signs of inflammation unless toxic doses of antigen were injected. In an attempt to promote intraocular DH, the AC's of MT-primed mice were pre-treated with subinflammatory intracameral injections of IFN-gamma, a cytokine that antagonizes TGF-beta, recruits antigen presenting cells (APC) from the blood and activates resident APC precursors. It was observed that AC injection of IFN-gamma, followed 3 days later by AC challenge with 200 ng of MT, resulted in severe intraocular inflammation only in primed (but not naive) mice. We conclude that the normal mouse AC resists DH unless its immunosuppressive microenvironment is abolished, as in these experiments by IFN-gamma. We propose that impaired expression of cell-mediated immunity is an important component of immune privilege of the AC.
Cousins
S W
SW
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, FL 33101.
Trattler
W B
WB
Streilein
J W
JW
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology* / Q000473:pathology; D003228:Conjunctiva / Q000276:immunology; D009877:Endophthalmitis / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000032:analysis; D007371:Interferon-gamma / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D011292:Premedication; D011994:Recombinant Proteins
D007074:Immunoglobulin G; D011994:Recombinant Proteins; D007371:Interferon-gamma