title: Control of advanced choroid plexus tumors in SV40 T antigen transgenic mice following priming of donor CD8(+) T lymphocytes by the endogenous tumor antigen.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. tds6@psu.edu
authors.forename: T D
authors.initials: TD
authors.lastname: Schell
authors.forename: S S
authors.initials: SS
authors.lastname: Tevethia
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics* / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016545:Choroid Plexus Neoplasms / Q000276:immunology* / Q000473:pathology; D003601:Cytotoxicity Tests, Immunologic; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation
chemical_list: D000952:Antigens, Polyomavirus Transforming; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma