TOLERANCE IN TCR COGNATE ANTIGEN DOUBLE-TRANSGENIC MICE MEDIATED BY INCOMPLETE THYMIC DELETION AND PERIPHERAL RECEPTOR DOWN-REGULATION

Influenza nucleoprotein (NP)-specific T-cell receptor transgenic mice (F5) were crossed with transgenic mice expressing the cognate antigeni c protein under the control of the H-2K(b) promoter. Double-transgenic mice show negative selection of thymocytes at the CD4(+)8(+)TCR(lo) t o CD4(+)8(+)TCR(hi) transition stage. A few CD8(+) T cells, however, e scape clonal deletion, and in the peripheral lymphoid organs of these mice, they exhibit low levels of the transgenic receptor and upregulat ed levels of the CD44 memory marker. Such cells do not proliferate upo n exposure to antigen stimulation in vivo or ex vivo, however, they ca n develop low but detectable levels of antigen-specific cytotoxic func tion after stimulation in vitro in the presence of IL-2.