Control of Advanced Choroid Plexus Tumors in SV40 T Antigen Transgenic Mice Following Priming of Donor CD8+ T Lymphocytes by the Endogenous Tumor Antigen

• Published in: The Journal of immunology (1950) Vol. 167; no. 12; pp. 6947 - 6956
• Main Authors: Schell, Todd D, Tevethia, Satvir S
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.12.2001
• Subjects: Adoptive Transfer; Animals; Antigens, Polyomavirus Transforming - genetics; Antigens, Polyomavirus Transforming - immunology; Brain - immunology; Brain - pathology; Cell Line; Cell Line, Transformed; Cells, Cultured; Choroid Plexus Neoplasms - immunology; Choroid Plexus Neoplasms - pathology; Cytotoxicity Tests, Immunologic; Disease Progression; Epitopes, T-Lymphocyte - immunology; Interferon-gamma - biosynthesis; Lymphocytes, Tumor-Infiltrating - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Spleen - immunology; Survival Rate; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - transplantation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.12.6947

Mouse models in which tumors arise spontaneously due to the transgenic expression of an oncoprotein provide an opportunity to test approaches that target the immune-mediated control of tumor progression. In this report we investigated the role of SV40 Tag-specific CD8(+) T cells in the control of advanced choroid plexus tumor progression using large tumor Ag (Tag) transgenic mice. Since mice of the SV11 line are tolerant to the immunodominant SV40 Tag-derived CTL epitopes, mice with advanced stage tumors were reconstituted with naive C57BL/6 spleen cells following a low dose of gamma-irradiation. This led to the priming of CTLs specific for the H2-K(b)-restricted epitope IV by the endogenous Tag and a significant increase in the life span of Tag transgenic mice. Epitope IV-specific CD8(+) T cells accumulated and persisted in the brains and tumors of SV11 mice, as determined by analysis with epitope-specific MHC class I tetramers. Brain-infiltrating epitope IV-specific T cells were capable of producing IFN-gamma as well as lysing syngeneic Tag-transformed cells in vitro. In addition, the adoptive transfer of spleen cells from Tag-immune C57BL/6 mice resulted in a dramatic increase in 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 brain. These results indicate that the control of advanced stage spontaneous choroid plexus tumors is associated with the induction of a strong and persistent CD8(+) T cell response to Tag.