Blocked negative selection of developing T cells in mice expressing the baculovirus p35 caspase inhibitor. |
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Authors: | M Izquierdo A Grandien L M Criado S Robles E Leonardo J P Albar G G de Buitrago and C Martínez-A |
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Institution: | Department of Immunology and Oncology, Centro Nacional de Biotecnología, UAM Campus de Cantoblanco, E-28049, Madrid, Spain. |
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Abstract: | Clonal deletion in the thymus by apoptosis is involved in purging the immune system of self-reactive T lymphocytes (negative selection). Cysteine proteases (caspases) belonging to the CPP32 family are activated during this process. We have produced transgenic mice expressing baculovirus p35, a broad-range caspase inhibitor. Thymocytes from p35 transgenic mice were resistant in vitro to several apoptosis-inducing agents; this resistance correlated with the inhibition of CPP32-like activity. Negative selection in vivo of thymocytes triggered by two exogenous antigens, staphylococcal enterotoxin B superantigen and an antigenic peptide in the F5 T-cell receptor transgenic model, was specifically inhibited in p35 transgenic mice. Our results provide direct evidence for caspase involvement in negative selection during thymocyte development. |
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