Cd8+ T Cells Targeting a Single Immunodominant Epitope are Sufficient for Elimination of Established Sv40 T Antigen-Induced Brain Tumors
Immunotherapy of established solid tumors is rarely achieved, and the mechanisms leading to success remain to be elucidated. We previously showed that extended control of advanced-stage autochthonous brain tumors is achieved following adoptive transfer of naive C57BL/6 splenocytes into sublethally irradiated line SV11 mice expressing the SV40 T Ag (T Ag) oncoprotein, and was associated with in vivo priming of CD8+ T cells (TCD8) specific for the dominant epitope IV (T Ag residues 404-411). Using donor lymphocytes derived from mice that are tolerant to epitope IV or a newly characterized transgenic mouse line expressing an epitope IV-specific TCR, we show that epitope IV-specific TCD8 are a necessary component of the donor pool and that purified naive epitope IV-specific TCD8 are sufficient to promote complete and rapid regression of established tumors. While transfer of naive TCR-IV cells alone induced some initial tumor regression, increased survival of tumor-bearing mice required prior conditioning of the host with a sublethal dose of gamma irradiation and was associated with complete tumor eradication. Regression of established tumors was associated with rapid accumulation of TCR-IV T cells within the brain following initial priming against the endogenous T Ag in the peripheral lymphoid organs. Additionally, persistence of functional TCR-IV cells in both the brain and peripheral lymphoid organs was associated with long-term tumor-free survival. Finally, we show that production of IFN-Î³, but not perforin or TNF-Î±, by the donor lymphocytes is critical for control of autochthonous brain tumors. © 2008 The American Association of Immunologists, Inc.
Tatum, Angela M.; Mylin, Lawrence M.; Bender, Susan J.; Fischer, Matthew A.; Vigliotti, Beth A.; Tevethia, M. Judith; Tevethia, Satvir S.; and Schell, Todd D., "Cd8+ T Cells Targeting a Single Immunodominant Epitope are Sufficient for Elimination of Established Sv40 T Antigen-Induced Brain Tumors" (2008). Educator Scholarship. 16.