Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection

Abstract CD4+ helper T cells and cytotoxic CD8+ T cells are key players for adaptive immune responses against acute infections with retroviruses. Similar to textbook knowledge the most important function of CD4+ T cells during an acute retrovirus infection seems to be their helper function for other...

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Autores principales:	Anna Malyshkina, Elisabeth Littwitz-Salomon, Kathrin Sutter, Gennadiy Zelinskyy, Sonja Windmann, Simone Schimmer, Annette Paschen, Hendrik Streeck, Kim J. Hasenkrug, Ulf Dittmer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e388d3a0c124baca7a9c26ec6d000a3
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spelling	oai:doaj.org-article:1e388d3a0c124baca7a9c26ec6d000a32021-12-02T16:05:59ZFas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection10.1038/s41598-017-08578-72045-2322https://doaj.org/article/1e388d3a0c124baca7a9c26ec6d000a32017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08578-7https://doaj.org/toc/2045-2322Abstract CD4+ helper T cells and cytotoxic CD8+ T cells are key players for adaptive immune responses against acute infections with retroviruses. Similar to textbook knowledge the most important function of CD4+ T cells during an acute retrovirus infection seems to be their helper function for other immune cells. Whereas there was no direct anti-viral activity of CD4+ T cells during acute Friend Virus (FV) infection, they were absolutely required for the control of chronic infection. During chronic FV infection a population of activated FV-specific CD4+ T cells did not express cytotoxic molecules, but Fas Ligand that can induce Fas-induced apoptosis in target cells. Using an MHC II-restricted in vivo CTL assay we demonstrated that FV-specific CD4+ T cells indeed mediated cytotoxic effects against FV epitope peptide loaded targets. CD4 + CTL killing was also detected in FV-infected granzyme B knockout mice confirming that the exocytosis pathway was not involved. However, killing could be blocked by antibodies against FasL, which identified the Fas/FasL pathway as critical cytotoxic mechanism during chronic FV infection. Interestingly, targeting the co-stimulatory receptor CD137 with an agonistic antibody enhanced CD4+ T cell cytotoxicity. This immunotherapy may be an interesting new approach for the treatment of chronic viral infections.Anna MalyshkinaElisabeth Littwitz-SalomonKathrin SutterGennadiy ZelinskyySonja WindmannSimone SchimmerAnnette PaschenHendrik StreeckKim J. HasenkrugUlf DittmerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Malyshkina Elisabeth Littwitz-Salomon Kathrin Sutter Gennadiy Zelinskyy Sonja Windmann Simone Schimmer Annette Paschen Hendrik Streeck Kim J. Hasenkrug Ulf Dittmer Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection
description	Abstract CD4+ helper T cells and cytotoxic CD8+ T cells are key players for adaptive immune responses against acute infections with retroviruses. Similar to textbook knowledge the most important function of CD4+ T cells during an acute retrovirus infection seems to be their helper function for other immune cells. Whereas there was no direct anti-viral activity of CD4+ T cells during acute Friend Virus (FV) infection, they were absolutely required for the control of chronic infection. During chronic FV infection a population of activated FV-specific CD4+ T cells did not express cytotoxic molecules, but Fas Ligand that can induce Fas-induced apoptosis in target cells. Using an MHC II-restricted in vivo CTL assay we demonstrated that FV-specific CD4+ T cells indeed mediated cytotoxic effects against FV epitope peptide loaded targets. CD4 + CTL killing was also detected in FV-infected granzyme B knockout mice confirming that the exocytosis pathway was not involved. However, killing could be blocked by antibodies against FasL, which identified the Fas/FasL pathway as critical cytotoxic mechanism during chronic FV infection. Interestingly, targeting the co-stimulatory receptor CD137 with an agonistic antibody enhanced CD4+ T cell cytotoxicity. This immunotherapy may be an interesting new approach for the treatment of chronic viral infections.
format	article
author	Anna Malyshkina Elisabeth Littwitz-Salomon Kathrin Sutter Gennadiy Zelinskyy Sonja Windmann Simone Schimmer Annette Paschen Hendrik Streeck Kim J. Hasenkrug Ulf Dittmer
author_facet	Anna Malyshkina Elisabeth Littwitz-Salomon Kathrin Sutter Gennadiy Zelinskyy Sonja Windmann Simone Schimmer Annette Paschen Hendrik Streeck Kim J. Hasenkrug Ulf Dittmer
author_sort	Anna Malyshkina
title	Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection
title_short	Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection
title_full	Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection
title_fullStr	Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection
title_full_unstemmed	Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection
title_sort	fas ligand-mediated cytotoxicity of cd4+ t cells during chronic retrovirus infection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1e388d3a0c124baca7a9c26ec6d000a3
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_version_	1718385133616103424

Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection

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