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Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of Autoimmunity

Apoptotic death of T lymphocytes is critical for shutdown of immune responses and hemopoietic cell homeostasis. Both death receptor (Fas) activation and mitochondrial apoptosis triggered by the BH3-only protein Bim have been implicated in the killing of antigen-stimulated T cells. We examined mice l...

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Autores principales: Hughes, Peter D., Belz, Gabrielle T., Fortner, Karen A., Budd, Ralph C., Strasser, Andreas, Bouillet, Philippe
Formato: Texto
Lenguaje:English
Publicado: Cell Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270348/
https://www.ncbi.nlm.nih.gov/pubmed/18275830
http://dx.doi.org/10.1016/j.immuni.2007.12.017
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author Hughes, Peter D.
Belz, Gabrielle T.
Fortner, Karen A.
Budd, Ralph C.
Strasser, Andreas
Bouillet, Philippe
author_facet Hughes, Peter D.
Belz, Gabrielle T.
Fortner, Karen A.
Budd, Ralph C.
Strasser, Andreas
Bouillet, Philippe
author_sort Hughes, Peter D.
collection PubMed
description Apoptotic death of T lymphocytes is critical for shutdown of immune responses and hemopoietic cell homeostasis. Both death receptor (Fas) activation and mitochondrial apoptosis triggered by the BH3-only protein Bim have been implicated in the killing of antigen-stimulated T cells. We examined mice lacking the gene encoding Bim (Bcl2l11) and with the inactivating lpr mutation in the gene encoding Fas (Fas), designated Bcl2l11(−/−)Fas(lpr/lpr) mice. Shutdown of an acute T cell response to herpes simplex virus involved only Bim with no contribution by Fas, whereas both pathways synergized in killing antigen-stimulated T cells in chronic infection with murine γ-herpesvirus. Bcl2l11(−/−)Fas(lpr/lpr) mice developed remarkably enhanced and accelerated fatal lymphadenopathy and autoimmunity compared to mice lacking only one of these apoptosis inducers. These results identify critical overlapping roles for Fas and Bim in T cell death in immune response shutdown and prevention of immunopathology and thereby resolve a long-standing controversy.
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spelling pubmed-22703482008-04-08 Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of Autoimmunity Hughes, Peter D. Belz, Gabrielle T. Fortner, Karen A. Budd, Ralph C. Strasser, Andreas Bouillet, Philippe Immunity Article Apoptotic death of T lymphocytes is critical for shutdown of immune responses and hemopoietic cell homeostasis. Both death receptor (Fas) activation and mitochondrial apoptosis triggered by the BH3-only protein Bim have been implicated in the killing of antigen-stimulated T cells. We examined mice lacking the gene encoding Bim (Bcl2l11) and with the inactivating lpr mutation in the gene encoding Fas (Fas), designated Bcl2l11(−/−)Fas(lpr/lpr) mice. Shutdown of an acute T cell response to herpes simplex virus involved only Bim with no contribution by Fas, whereas both pathways synergized in killing antigen-stimulated T cells in chronic infection with murine γ-herpesvirus. Bcl2l11(−/−)Fas(lpr/lpr) mice developed remarkably enhanced and accelerated fatal lymphadenopathy and autoimmunity compared to mice lacking only one of these apoptosis inducers. These results identify critical overlapping roles for Fas and Bim in T cell death in immune response shutdown and prevention of immunopathology and thereby resolve a long-standing controversy. Cell Press 2008-02-15 /pmc/articles/PMC2270348/ /pubmed/18275830 http://dx.doi.org/10.1016/j.immuni.2007.12.017 Text en © 2008 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Hughes, Peter D.
Belz, Gabrielle T.
Fortner, Karen A.
Budd, Ralph C.
Strasser, Andreas
Bouillet, Philippe
Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of Autoimmunity
title Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of Autoimmunity
title_full Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of Autoimmunity
title_fullStr Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of Autoimmunity
title_full_unstemmed Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of Autoimmunity
title_short Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of Autoimmunity
title_sort apoptosis regulators fas and bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270348/
https://www.ncbi.nlm.nih.gov/pubmed/18275830
http://dx.doi.org/10.1016/j.immuni.2007.12.017
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