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. 1999 Jan 4;18(1):156–166. doi: 10.1093/emboj/18.1.156

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

M Izquierdo 1, A Grandien 1, L M Criado 1, S Robles 1, E Leonardo 1, J P Albar 1, G G de Buitrago 1, C Martínez-A 1
PMCID: PMC1171111  PMID: 9878059

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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Selected References

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