Blocked negative selection of developing T cells in mice expressing the baculovirus p35 caspase inhibitor.
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.
Izquierdo
M
M
Department of Immunology and Oncology, Centro Nacional de Biotecnología, UAM Campus de Cantoblanco, E-28049, Madrid, Spain.
Grandien
A
A
Criado
L M
LM
Robles
S
S
Leonardo
E
E
Albar
J P
JP
de Buitrago
G G
GG
Martínez-A
C
C
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D017209:Apoptosis; D001483:Base Sequence; D053148:Caspase 3; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D051034:Inhibitor of Apoptosis Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D017924:Nucleopolyhedroviruses / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics*
D000941:Antigens; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C505409:Casp3 protein, mouse; D053148:Caspase 3