Immune Privileged

While this question may seem obvious, the critical experiments required to answer it have not been performed. There are several approaches to address this question. In one series of experiments, either normal or immunocompromised mice would receive an intraocular dose of a chemical carcinogen such as MCA. If immune surveillance occurs within the eye, then the incidence of tumors will increase in the immune-compromised mice. If immune surveillance does not occur within the eye, then the incidence of tumors will not change in the absence of an intact immune response. It will be important to examine a variety of innate and adaptive immunodeficient mice in order to determine if immune surveillance occurs within the eye.

A second type of experiment would utilize the recently developed trans-genic models that spontaneously develop either retinoblastoma, or uveal melanoma [32, 33]. These transgenic mice would be crossed with immunodefi-cient mice, and the speed and size of tumor development would be monitored. If immune surveillance occurs in the eye, then the spontaneous tumors will appear sooner and grow more rapidly. If immune surveillance does not occur, then the appearance of the spontaneous tumors will remain unchanged. These experiments would conclusively prove whether immune surveillance occurs within the immune-privileged eye.

A third type of experiment would conclusively prove a close association between immune privilege and immune surveillance. In these experiments, MCA would be used to induce tumors in the eyes of immunocompetent mice in which immune privilege is terminated. If the frequency of tumors decreases in the absence of immune privilege in immunocompetent mice, then this will demonstrate that immune privilege blocks immune surveillance in the eye. The technical problem with conducting this type of experiment is that immune privilege would have to be terminated for many months in order to induce tumors with MCA. Currently, there is no method of terminating immune privilege in the eye for extended periods of time. However, the recent discovery of defects in immune privilege and anterior chamber-associated immune deviation in DBA/2J mice may provide the opportunity to conduct this type of experiment [34].

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