Bad can act as a key regulator of T cell apoptosis and T cell development

• Published in: The Journal of experimental medicine Vol. 189; no. 3; pp. 575 - 586
• Main Authors: Mok, C L, Gil-Gómez, G, Williams, O, Coles, M, Taga, S, Tolaini, M, Norton, T, Kioussis, D, Brady, H J
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 01.02.1999
• Subjects: Animals; Apoptosis; bcl-Associated Death Protein; Carrier Proteins - biosynthesis; CD3 Complex - metabolism; Cell Cycle; Dexamethasone - pharmacology; fas Receptor - immunology; Gamma Rays - adverse effects; Homeodomain Proteins - genetics; Interleukin-12 - biosynthesis; Mice; Mice, Transgenic; Phosphatidylinositol 3-Kinases - metabolism; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Signal Transduction; T-Lymphocytes - immunology; Thymus Gland - cytology; Thymus Gland - immunology; Up-Regulation
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.189.3.575

Bad is a distant relative of Bcl-2 and acts to promote cell death. Here, we show that Bad expression levels are greatly increased in thymocytes during apoptosis. We generated bad transgenic mice to study the action of upregulated Bad expression on T cell apoptosis. The T cells from these mice are highly sensitive to apoptotic stimuli, including anti-CD95. The numbers of T cells are greatly depleted and the processes of T cell development and selection are perturbed. We show that the proapoptotic function of Bad in primary T cells is regulated by Akt kinase and that Bad overexpression enhances both cell cycle progression and interleukin 2 production after T cell activation. These data suggest that Bad can act as a key regulator of T cell apoptosis and that this is a consequence of its upregulation after exposure to death stimuli.