Tolerance in TCR/Cognate Antigen Double-Transgenic
Mice Mediated by Incomplete Thymic Deletion and
Peripheral Receptor Downregulation |
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| Authors: | Clio Mamalaki Marianna Murdjeva Mauro Tolaini Trisha Norton Phillip Chandler Alain Townsend Elizabeth Simpson Dimitris Kioussis |
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| Institution: | 1. lnstitute of Molecular Biology and Biotechnology, Crete, Greece.;2. Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom.;3. MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, W12 ONN, United Kingdom.;4. Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom, |
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| Abstract: | 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+TCR10 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. |
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| Keywords: | Tolerance deletion F5 TCR nucleoprotein double-transgenic mice |
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