The immune-mediated rejection of intraocular tumors is associated with two very different patterns of ocular pathology (1) tumor rejection accompanied by destruction of the eye and (2) non- destructive tumor rejection that leaves the basic anatomical structures of the eye intact. At least two types of immune effector cells are thought to participate in the immune-mediated rejection of tumors: cytotoxic T cells (Tc) and mediators of delayed hypersensitivity (Tdh). There is reason to suspect that the Tc and Tdh effector cells that participate in the rejection of ocular tumors may also be important in determining the type of ocular pathology that accompanies tumor rejection. To determine what effector cells are present within the eye during tumor rejection, we developed a technique to recover lymphocytes from tumor-containing mouse eyes. These tumor-infiltrating lymphocytes can then be assayed for Tc and Tdh effector functions. This proposed research examines the differences in the Tc and Tdh immune effector cells that are present within the eye during three patterns of tumor growth: (1) progressive tumor growth (2) tumor rejection and destruction of the eye and (3) Non-destructive tumor rejection. We hypothesize that the precision with which the intraocular tumors are rejected is dependent upon the developing tumor burden and the rapidity with which tumor-specific delayed hypersensitivity is expressed locally.
The specific aims of this research are: (1) Identify and characterize the immune effector and regulatory cells that are present within the eye during the three patterns of tumor growth. (2) Provide direct evidence that the immune effector and regulatory cells, identified within the eye, are indeed responsible for the clearance of the tumor cells and the coincident ocular pathology. (3) Determine the quantitative relationship between the degree of allogenicity of the tumor cells inoculated into the anterior chamber of the eye and (a) the resulting pattern of ocular tumor growth and (b) the response of Tc and Tdh effector cells.
