Cargando…
CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice
The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen‐presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T‐cell receptor complex a plethora of c...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980220/ https://www.ncbi.nlm.nih.gov/pubmed/29281850 http://dx.doi.org/10.1111/imm.12884 |
_version_ | 1783327850058743808 |
---|---|
author | Bathke, Barbara Pätzold, Juliane Kassub, Ronny Giessel, Raphael Lämmermann, Kerstin Hinterberger, Maria Brinkmann, Kay Chaplin, Paul Suter, Mark Hochrein, Hubertus Lauterbach, Henning |
author_facet | Bathke, Barbara Pätzold, Juliane Kassub, Ronny Giessel, Raphael Lämmermann, Kerstin Hinterberger, Maria Brinkmann, Kay Chaplin, Paul Suter, Mark Hochrein, Hubertus Lauterbach, Henning |
author_sort | Bathke, Barbara |
collection | PubMed |
description | The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen‐presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T‐cell receptor complex a plethora of co‐stimulatory signals not only ensures a proper T‐cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The tumour necrosis factor receptor/ligand pair CD27/CD70 gained a lot of attention because of its key role in regulating T‐cell activation, survival, differentiation and maintenance, especially in the course of viral infections and cancer. We sought to investigate the role of CD70 co‐stimulation for immune responses induced by the vaccine vector modified vaccinia virus Ankara–Bavarian Nordic(®) (MVA‐BN (®)). Short‐term blockade of CD70 diminished systemic CD8 T‐cell effector and memory responses in mice. The dependence on CD70 became even more apparent in the lungs of MHC class II‐deficient mice. Importantly, genetically encoded CD70 in MVA‐BN (®) not only increased CD8 T‐cell responses in wild‐type mice but also substituted for CD4 T‐cell help. MHC class II‐deficient mice that were immunized with recombinant MVA‐CD70 were fully protected against a lethal virus infection, whereas MVA‐BN (®)‐immunized mice failed to control the virus. These data are in line with CD70 playing an important role for vaccine‐induced CD8 T‐cell responses and prove the potency of integrating co‐stimulatory molecules into the MVA‐BN (®) backbone. |
format | Online Article Text |
id | pubmed-5980220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59802202018-06-06 CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice Bathke, Barbara Pätzold, Juliane Kassub, Ronny Giessel, Raphael Lämmermann, Kerstin Hinterberger, Maria Brinkmann, Kay Chaplin, Paul Suter, Mark Hochrein, Hubertus Lauterbach, Henning Immunology Original Articles The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen‐presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T‐cell receptor complex a plethora of co‐stimulatory signals not only ensures a proper T‐cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The tumour necrosis factor receptor/ligand pair CD27/CD70 gained a lot of attention because of its key role in regulating T‐cell activation, survival, differentiation and maintenance, especially in the course of viral infections and cancer. We sought to investigate the role of CD70 co‐stimulation for immune responses induced by the vaccine vector modified vaccinia virus Ankara–Bavarian Nordic(®) (MVA‐BN (®)). Short‐term blockade of CD70 diminished systemic CD8 T‐cell effector and memory responses in mice. The dependence on CD70 became even more apparent in the lungs of MHC class II‐deficient mice. Importantly, genetically encoded CD70 in MVA‐BN (®) not only increased CD8 T‐cell responses in wild‐type mice but also substituted for CD4 T‐cell help. MHC class II‐deficient mice that were immunized with recombinant MVA‐CD70 were fully protected against a lethal virus infection, whereas MVA‐BN (®)‐immunized mice failed to control the virus. These data are in line with CD70 playing an important role for vaccine‐induced CD8 T‐cell responses and prove the potency of integrating co‐stimulatory molecules into the MVA‐BN (®) backbone. John Wiley and Sons Inc. 2018-01-26 2018-06 /pmc/articles/PMC5980220/ /pubmed/29281850 http://dx.doi.org/10.1111/imm.12884 Text en © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Bathke, Barbara Pätzold, Juliane Kassub, Ronny Giessel, Raphael Lämmermann, Kerstin Hinterberger, Maria Brinkmann, Kay Chaplin, Paul Suter, Mark Hochrein, Hubertus Lauterbach, Henning CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice |
title |
CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice |
title_full |
CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice |
title_fullStr |
CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice |
title_full_unstemmed |
CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice |
title_short |
CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice |
title_sort | cd70 encoded by modified vaccinia virus ankara enhances cd8 t‐cell‐dependent protective immunity in mhc class ii‐deficient mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980220/ https://www.ncbi.nlm.nih.gov/pubmed/29281850 http://dx.doi.org/10.1111/imm.12884 |
work_keys_str_mv | AT bathkebarbara cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT patzoldjuliane cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT kassubronny cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT giesselraphael cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT lammermannkerstin cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT hinterbergermaria cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT brinkmannkay cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT chaplinpaul cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT sutermark cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT hochreinhubertus cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice AT lauterbachhenning cd70encodedbymodifiedvacciniavirusankaraenhancescd8tcelldependentprotectiveimmunityinmhcclassiideficientmice |