Control of advanced choroid plexus tumors in SV40 T antigen transgenic mice following priming of donor CD8(+) T lymphocytes by the endogenous tumor antigen

Mouse models in which tumors arise spontaneously due to the transgenic expr ession of an oncoprotein provide an opportunity to test approaches that tar get the immune-mediated control of tumor progression. In this report we inv estigated the role of SV40 Tag-specific CD8(+) T cells in the control of ad vanced choroid plexus tumor progression using large tumor Ag (Tag) transgen ic mice. Since mice of the SV11 line are tolerant to the immunodominant SV4 0 Tag-derived CTL epitopes, mice with advanced stage tumors were reconstitu ted with naive C57BL/6 spleen cells following a low dose of gamma -irradiat ion. This led to the priming of CTLs specific for the H2-K-b-restricted epi tope IV by the endogenous Tag and a significant increase in the life span o f Tag transgenic mice. Epitope IV-specific CD8(+) T cells accumulated and p ersisted in the brains and tumors of SV11 mice, as determined by analysis w ith epitope-specific MHC class I tetramers. Brain-infiltrating epitope IV-s pecific T cells were capable of producing IFN-gamma as well as lysing synge neic Tag-transformed cells in vitro. In addition, the adoptive transfer of spleen cells from Tag-immune C57BL/6 mice resulted in a dramatic increase i n the control of tumor progression in SV11 mice and was associated with the accumulation of CD8(+) T cells specific for multiple Tag epitopes in the b rain. These results indicate that the control of advanced stage spontaneous choroid plexus tumors is associated with the induction of a strong and per sistent CD8(+) T cell response to Tag.