Tolerance in TCR/cognate antigen double-transgenic mice mediated by incomplete thymic deletion and peripheral receptor downregulation.

Influenza nucleoprotein (NP)-specific T-cell receptor transgenic mice (F5) were crossed with transgenic mice expressing the cognate antigenic protein under the control of the H-2Kb promoter. Double-transgenic mice show negative selection of thymocytes at the CD4+8+TCRlo to CD4+8+TCRhi transition stage. A few CD8+ T cells, however, escape clonal deletion, and in the peripheral lymphoid organs of these mice, they exhibit low levels of the transgenic receptor and upregulated levels of the CD44 memory marker. Such cells do not proliferate upon exposure to antigen stimulation in vivo or ex vivo, however, they can develop low but detectable levels of antigen-specific cytotoxic function after stimulation in vitro in the presence of IL-2.