The NF-kappa B regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cells
Details
Publication Year 2006-07-18,Volume 103,Issue #29,Page 10979-10984
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type
Journal Article
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(-/-) 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.
Publisher
NATL ACAD SCIENCES
Keywords
FAMILY-MEMBER BIM; APOPTOTIC RESPONSES; MOTOR COMPLEX; IN-VIVO; EXPRESSION; SURVIVAL; INDUCTION; NOXA; TRANSCRIPTION; INFECTION
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Creation Date: 2006-07-18 12:00:00
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