BH3-only protein Puma contributes to death of antigen-specific T cells during shutdown of an immune response to acute viral infection
- Author(s)
- Fischer, SF; Belz, GT; Strasser, A;
- Details
- Publication Year 2008-02-26,Volume 105,Issue #8,Page 3035-3040
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- During acute T cell immune responses to viral infection, antigenspecific T cells first proliferate and differentiate into effector cells, but after pathogen clearance most are deleted by apoptosis. The developmentally programmed death of antigen-specific T cells during shutdown of a T cell response is mediated by the Bcl-2regulated apoptotic pathway and partly depends on the proapoptotic BH3-only protein Bim. However, loss of Bim enhanced survival of antigen-activated T cells to a lesser extent than Bcl-2 overexpression, indicating that other proapoptotic factors must contribute to T cell killing. In this study, we investigated the contributions of several BH3-only proteins to the shutdown of an acute T cell immune response in vivo. After infection with human herpes simplex virus (HSV-1), mice lacking Noxa, Bid, or Bad had a normal increase and subsequent decline in the numbers of antigenspecific CD8(+) T cells. In contrast, Puma-deficient mice showed an abnormally prolonged persistence of antigen-specific CD8(+) T cells in the spleen, associated with enhanced in vitro survival of these cells in the absence of cytokines. Puma was dispensable for viral clearance and also did not play a role in proliferation or activation of HSV-1-specific CD8(+) T cells in vivo. Collectively, these findings show that Puma contributes to the death of antigen-specific T cells during shutdown of an immune response.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- FAMILY-MEMBER BIM; BCL-2 FAMILY; IN-VIVO; APOPTOTIC RESPONSES; SURVIVAL; BAX; MICE; DELETION; PATHWAYS; NOXA
- Publisher's Version
- https://doi.org/10.1073/pnas.0706913105
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2008-02-26 12:00:00