ANALYSIS OF IMMUNE DEVIATION ELICITED BY ANTIGENS INJECTED INTO THE SUBRETINAL SPACE

PURPOSE. To determine whether the subretinal space supports the induct ion of deviant immune responses to cell-associated and soluble antigen s and to elucidate factors influencing the immunologic properties of t he subretinal space. METHODS. P815 mastocytoma cells were used as cell -associated antigens and were inoculated into the anterior chamber (AC ), the vitreous cavity (VC), the subretinal space, and subconjunctival ly in H2-compatible, but minor H-incompatible, BALB/c mice. Ovalbumin, as a soluble antigen, was similarly injected into eyes, after which r ecipient animals were immunized with ovalbumin and complete Freund's a djuvant. Delayed-type hypersensitivity (DTH) was assessed by ear chall enge. To alter the conditions in the subretinal space, the outer blood -retinal barrier was disrupted by compromising retinal pigment epithel ial (RPE) cells with a systemic injection of sodium iodate. Immune pri vilege in the AC was abolished by mild corneal cauterization. RESULTS. Antigen-specific DTH did not develop in mice in which alloantigenic t umor cells or ovalbumin was injected into the AC, the VC, or the subre tinal space, and the mice's spleens contained lymphocytes capable of s uppressing DTH when adoptively transferred into naive mice. When RPE c ells were compromised with sodium iodate, tumor cells or ovalbumin inj ected into the subretinal space or the VC did not induce immune deviat ion, although the AC of these eyes still promoted AC-associated immune deviation. By contrast, when immune privilege in the AC was abolished by corneal cauterization, neither tumor cells nor ovalbumin injected into the subretinal space or the VC of eyes elicited immune deviation. CONCLUSIONS. The subretinal space supports immune deviation for histo incompatible tumor cells and soluble protein antigens by actively supp ressing antigen-specific DTH. Acute loss of immune privilege in the su bretinal space and the VC does not cause loss of privilege in the AC, but abolition of immune privilege in the AC eliminates the capacity of the subretinal space and the VC to support immune deviation to antige ns injected locally..