First Author | Bauer A | Year | 2006 |
Journal | Proc Natl Acad Sci U S A | Volume | 103 |
Issue | 29 | Pages | 10979-84 |
PubMed ID | 16832056 | Mgi Jnum | J:111822 |
Mgi Id | MGI:3654888 | Doi | 10.1073/pnas.0603625103 |
Citation | Bauer A, et al. (2006) The NF-kappaB regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cells. Proc Natl Acad Sci U S A 103(29):10979-84 |
abstractText | 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-kappaB regulator Bcl-3 and the proapoptotic Bcl-2 family members Bim and Puma. Bcl-3 overexpression increased survival, and activated bcl-3-/- 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-/- 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-/- and noxa-/- 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. |