Control of Syngeneic Tumor Growth by Activation of CD8+ T Cells: Efficacy Is Limited by Migration Away from the Site and Induction of Nonresponsiveness

摘要: Activation of Ag-specific CD8+ T cells in response to syngeneic tumor has been visualized by adoptive transfer from OT-I mice, with a transgenic TCR specific for H-2Kb and an OVA peptide, into Thy-1 congenic recipients. Intraperitoneal challenge E.G7, the EL-4 thymoma transfected OVA, results activation clonal expansion peritoneal cavity transient control growth. However, within 2 days after becoming activated, migrate out spleen lymph nodes, growth resumes cavity. The nodes have lytic effector activity, but exhibit split anergy that they cannot proliferate Ag unless exogenous IL-2 is provided. failure remain at site continue not due selection loss variants or development suppression. These suggest effective CD8-targeted immunotherapy may depend less on enhancing initial more sustaining appropriate location and/or reactivating left become nonresponsive.