Tolerance in TCR/Cognate Antigen Double-TransgenicMice Mediated by Incomplete Thymic Deletion andPeripheral Receptor Downregulation

摘要

Influenza nucleoprotein (NP)-specific T-cell receptor transgenic mice (F5) were crossedwith transgenic mice expressing the cognate antigenic protein under the control of the H-2Kbpromoter. Double-transgenic mice show negative selection of thymocytes at theCD4+8+TCR10to CD4+8+TCRhitransition stage. A few CD8 T cells, however, escape clonaldeletion, and in the peripheral lymphoid organs of these mice, they exhibit low levels ofthe transgenic receptor and upregulated levels of the CD44 memory marker. Such cells donot proliferate upon exposure to antigen stimulationin vivoorex vivo, however, they candevelop low but detectable levels of antigen-specific cytotoxic function after stimulationin vitroin the presence of IL-2.