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Blocked negative selection of developing T cells in mice expressing the baculovirus p35 caspase inhibitor
Author(s) -
Izquierdo M.,
Grandien A.,
Criado L.M.,
Robles S.,
Leonardo E.,
Albar J.P.,
de Buitrago G.González,
MartínezA C.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.1.156
Subject(s) - library science , oncology , humanities , biology , medicine , art , computer science
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.