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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-08578-7 |
| _version_ | 1818427505907859456 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T14:46:48Z |
| format | Article |
| id | doaj.art-1e388d3a0c124baca7a9c26ec6d000a3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T14:46:48Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1e388d3a0c124baca7a9c26ec6d000a32022-12-21T22:57:15ZengNature PortfolioScientific Reports2045-23222017-08-017111010.1038/s41598-017-08578-7Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infectionAnna Malyshkina0Elisabeth Littwitz-Salomon1Kathrin Sutter2Gennadiy Zelinskyy3Sonja Windmann4Simone Schimmer5Annette Paschen6Hendrik Streeck7Kim J. Hasenkrug8Ulf Dittmer9Institute for Virology, University Hospital Essen, University of Duisburg-EssenInstitute for Virology, University Hospital Essen, University of Duisburg-EssenInstitute for Virology, University Hospital Essen, University of Duisburg-EssenInstitute for Virology, University Hospital Essen, University of Duisburg-EssenInstitute for Virology, University Hospital Essen, University of Duisburg-EssenInstitute for Virology, University Hospital Essen, University of Duisburg-EssenDepartment of Dermatology, Venereology, and Allergology, University Hospital Essen, University of Duisburg-EssenInstitute for HIV Research, University Hospital Essen, University Duisburg-EssenLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of HealthInstitute for Virology, University Hospital Essen, University of Duisburg-EssenAbstract 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.https://doi.org/10.1038/s41598-017-08578-7 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-08578-7 |
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