Peripheral tolerance in mice expressing a liver-specific class I molecule: inactivation/deletion of a T-cell subpopulation.
We previously demonstrated that C3H/HeJ transgenic (TG) mice that express a laboratory-engineered class I molecule, Q10/L, exclusively on liver parenchymal cells show no evidence of hepatic disease even after deliberate immunization. Nevertheless, these animals demonstrate cytotoxic T-lymphocyte (CTL) activity specific for Q10/L, although it is less than that obtained from non-TG littermates. We now show that this decrease in CTL activity is not a reflection of a decrease in precursors, since both TG and normal animals have similar numbers. When non-TG C3H mice are primed with H-2Ld and H-2Kbm1 antigens, which extensively crossreact with Q10/L, their specific in vitro CTL activity directed against H-2Ld, H-2Kbm1, and Q10/L is increased 10- to 20-fold, as expected. Although primed TG mice show similar increases in in vitro CTL activity directed against H-2Ld and H-2Kbm1, they display no increase in anti-Q10/L activity. Whereas anti-H-2Ld spleen cells from non-TG mice readily generate CTL lines and clones specific for H-2Ld and Q10/L, TG cells give rise to anti-H-2Ld lines or clones only. These data indicate that the tolerance in TG mice is accounted for by the inactivation or deletion of an important CTL subpopulation having the capability of recognizing the peripheral antigen in situ. To determine whether tolerance would persist in the absence of Q10/L, TG cells were transferred into non-TG recipients. Three weeks later Q10/L-specific lytic activity generated in in vitro bulk cultures remained reduced compared to non-TG cells, indicating that the tolerant phenotype was stable during this interval.
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas.
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Jones-Youngblood
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Forman
D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D008099:Liver / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015395:Histocompatibility Antigens Class I