REJECTION OF INTRAOCULAR TUMORS FROM TRANSGENIC MICE BY TUMOR-INFILTRATING LYMPHOCYTES

The present study examined the role of tumor infiltrating lymphocytes (TIL) in the rejection of intraocular tumors from SV40 transgenic mice . Tumor cells from an intraocular tumor arising in an SV40 transgenic FVB/N mouse were transplanted into the eyes of syngeneic FVB/N mice an d the TIL isolated. TIL were assessed for direct cytolytic activity in vitro. TIL were also transferred passively to immunosuppressed FVB/N mice to determine if they could mediate intraocular tumor rejection. T he role of CD4(+) and CD8(+) T cells in intraocular tumor rejection wa s evaluated by depleting the respective cell populations in FVB/N host s prior to intraocular tumor challenge. The results showed that intrao cular tumors undergoing rejection in immunocompetent syngeneic hosts b ecame infiltrated with T cells, with the CD8(+) subset predominating a t the time of rejection. By contrast, athymic nude mice did not reject the intraocular tumors nor did the tumors become infiltrated with TIL . TIL displayed direct, tumor-specific cytolytic activity immediately after isolation from the tumor-containing eyes. FVB/N hosts depleted o f CD4(+) T cells were unable to reject their intraocular tumors. In vi vo depletion of CD8(+) T cells delayed, but did not prevent tumor reje ction. Adoptively transferred TIL mediated swift rejection of intraocu lar tumors in immunoincompetent recipients. Recipients of TIL, but not recipients of normal spleen cells, acquired significant tumor-specifi c CTL activity that was demonstrable in vitro. The results strongly su ggest, but do not prove, that TIL mediate rejection of intraocular tum ors from transgenic mice by direct cytolysis. Although CD4(+) T cells are necessary for tumor rejection and are capable of direct cytolysis, the predominant effector cells are CD8(+) CTL.