Inhibitor of Apoptosis Protein from Orgyia pseudotsugata Nuclear Polyhedrosis Virus Provides a Costimulatory Signal Required for Optimal Proliferation of Developing Thymocytes

• Published in: The Journal of immunology (1950) Vol. 168; no. 4; pp. 1770 - 1779
• Main Authors: Robles, Maria S, Leonardo, Esther, Criado, Luis Miguel, Izquierdo, Manuel, Martinez-A., Carlos
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.02.2002
• Subjects: Animals; Apoptosis; Baculovirus; CD3 Complex - metabolism; Cells, Cultured; Cytokines - biosynthesis; DNA-Binding Proteins - metabolism; I-kappa B Proteins; I^KB^a protein; IAP protein; IBa protein; Inhibitor of Apoptosis Proteins; Lymphocyte Activation; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - genetics; Mice; Mice, Transgenic; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Nuclear polyhedrosis virus; Nucleopolyhedrovirus; Orgyia pseudotsugata; Promoter Regions, Genetic; Proteins - genetics; Receptors, Antigen, T-Cell - antagonists & inhibitors; Receptors, Antigen, T-Cell - metabolism; Signal Transduction; T-Lymphocytes - immunology; Thymus Gland - growth & development; Thymus Gland - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.4.1770

The inhibitors of apoptosis proteins (IAPs) constitute a family of endogenous inhibitors that control apoptosis in the cell by inhibiting caspase processing and activity. IAPs are also implicated in cell division, cell cycle regulation, and cancer. To address the role of IAPs in thymus development and homeostasis, we generated transgenic mice expressing IAP generated from the baculovirus Orgyia pseudotsugata nuclear polyhedrosis virus (OpIAP). Developing thymocytes expressing OpIAP show increased nuclear levels of NF-kappaB and reduced cytoplasmic levels of its inhibitor, IkappaBalpha. In mature thymocytes, OpIAP induces optimal activation and proliferation after TCR triggering in the absence of a costimulatory signal. OpIAP expression in immature thymocytes blocks TCR-induced apoptosis. Taken together, our data illustrate the pleiotropism of OpIAP in vivo.