Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 8, Pages 3035-3040Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0706913105
Keywords
apoptosis; bim; T lymphocytes
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Funding
- NCI NIH HHS [R01 CA080188, CA 80188, CA 43540, R01 CA043540] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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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.
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