Open AccessBH3-only protein Puma contributes to death of antigen-specific T cells during shutdown of an immune response to acute viral infection
Author(s) -
Silke Fischer,
Gabrielle T. Belz,
Andreas Strasser
Publication year - 2008
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0706913105
Subject(s) - immune system , puma , biology , antigen , cd8 , t cell , immunology , cytotoxic t cell , programmed cell death , apoptosis , microbiology and biotechnology , virology , in vitro , biochemistry
During acute T cell immune responses to viral infection, antigen-specific 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-2-regulated 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 responsein 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 antigen-specific CD8+ T cells. In contrast, Puma-deficient mice showed an abnormally prolonged persistence of antigen-specific CD8+ T cells in the spleen, associated with enhancedin 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 cellsin vivo . Collectively, these findings show that Puma contributes to the death of antigen-specific T cells during shutdown of an immune response.