BH3-only protein Puma contributes to death of antigen-specific T cells during shutdown of an immune response to acute viral infection.
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 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 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 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.
Fischer
Silke F
SF
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne VIC 3050, Australia.
Belz
Gabrielle T
GT
Strasser
Andreas
A
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006561:Herpes Simplex / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000276:immunology*
D051017:Apoptosis Regulatory Proteins; C488588:PUMA protein, mouse; D025521:Tumor Suppressor Proteins