Rejection of intraocular tumors by CD4(+) T cells without induction of phthisis

Immune privilege of the eye protects against sight-threatening inflammatory events, but can also permit outgrowth of otherwise nonlethal immunogenic t umors. Nonetheless, ocular tumor growth can be controlled by cellular immun e responses. However, this will normally result in phthisis of the eye, in case tumor rejection is mediated by a delayed-type hypersensitivity respons e orchestrated by CD4(+) T cells. We now show that intraocular tumors can b e eradicated by CD4(+) Th cells without inducing collateral damage of neigh boring ocular tissue. Injection of tumor cells transformed by the early reg ion I of human adenovirus type 5 in the anterior chamber of the eye leads t o intraocular tumor formation. Tumor growth is transient in immunocompetent mice, but lethal in immunodeficient nude mice, indicating that T cell-depe ndent immunity is responsible for tumor clearance. Tumor rejection has all the characteristics of a CD8(+) T cell-mediated immune response, as the tum or did not express MHC class II and only tumor tissue was the subject of de struction. However, analysis of the molecular and cellular mechanisms invol ved in tumor clearance revealed that perforin, TNF-alpha, Fas ligand, MHC c lass I, and CD8(+) T cells did not play a crucial role in tumor eradication . Instead, effective tumor rejection was entirely dependent on CD4(+) Th ce lls, as CD4-depleted as well as MHC class II-deficient mice were unable to reject their intraocular tumor. Taken together, these observations demonstr ate that CD4(+) T cells are able to eradicate MHC class U-negative tumors i n an immune-privileged site without affecting surrounding tissues or the in duction of phthisis.