1. The NF-[kappa]B regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cells
- Author
-
Bauer, Anette, Villunger, Andreas, Labi, Verena, Fischer, Silke F., Strasser, Andreas, Wagner, Hermann, Schmid, Roland M., and Hacker, Georg
- Subjects
Apoptosis -- Research ,T cells -- Research ,Cytokines -- Research ,Science and technology - Abstract
Apoptosis of activated T cells is critical for the termination of immune responses. Here we show that adjuvant-stimulated dendritic cells secrete cytokines that prime activated T cells for survival and analyze the roles of the NF-[kappa]B regulator Bcl-3 and the proapoptotic Bcl-2 family members Bim and Puma. Bcl-3 overexpression increased survival, and activated bcl-[3.sup.-/-] T cells died abnormally rapidly. Cytokines from adjuvant-stimulated dendritic cells induced Bcl-3, but survival through cytokine priming was Bcl-3-independent. Apoptosis inhibition by Bcl-3 involved blockade of Bim activation, because Bim was overactivated in Bcl-3-deficient cells, and Bcl-3 failed to increase survival of [bim.sup.-/-] T cells. However, adjuvants increased survival also in Bim-deficient T cells. This Bim-independent death pathway is at least in part regulated by Puma, as shown by analysis of [puma.sup.-/-] and [noxa.sup.-/-] T cells. IL-1, IL-7, and IL-15 primed T cells for survival even in the absence of Bim or Puma. Our data define interrelations and a Bim-independent pathway to activated T cell death. adjuvant | apoptosis | Bcl-2-family | survival
- Published
- 2006