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Blocked negative selection of developing T cells in mice expressing the baculovirus p35 caspase inhibitor

AuthorsIzquierdo, Manuel ; Grandien, A.; Criado, Luis M.; Robles, S.; Leonardo, Esther; Albar, Juan Pablo; González de Buitrago, Gonzalo; Martínez-Alonso, Carlos
KeywordsBaculovirus p35
Negative selection
Issue Date1999
PublisherEuropean Molecular Biology Organization
CitationEMBO Journal 18(1): 156-166 (1999)
AbstractClonal 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.
Publisher version (URL)https://doi.org/10.1093/emboj/18.1.156
Appears in Collections:(CNB) Artículos
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