Chronic viral infections impinge on naive bystander CD8 T cells
Abstract Introduction Epidemiological data suggest that persistent viral infections impair immune homeostasis and immune responsiveness. Previous studies showed that chronic virus infections negatively impact bystander T‐cell differentiation and memory formation but there is limited knowledge of how...
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Online Access: | https://doi.org/10.1002/iid3.300 |
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doaj-fe8f9d3220d148f9af28f4c72b63cf822020-11-25T03:32:23ZengWileyImmunity, Inflammation and Disease2050-45272020-09-018324925710.1002/iid3.300Chronic viral infections impinge on naive bystander CD8 T cellsIsabel Barnstorf0Suzanne P. M. Welten1Mariana Borsa2Nicolas S. Baumann3Katharina Pallmer4Nicole Joller5Roman Spörri6Annette Oxenius7Institute of Microbiology, Department of Biology ETH Zürich Zürich SwitzerlandInstitute of Microbiology, Department of Biology ETH Zürich Zürich SwitzerlandInstitute of Microbiology, Department of Biology ETH Zürich Zürich SwitzerlandInstitute of Microbiology, Department of Biology ETH Zürich Zürich SwitzerlandInstitute of Microbiology, Department of Biology ETH Zürich Zürich SwitzerlandInstitute of Experimental Immunology University of Zürich Zürich SwitzerlandInstitute of Microbiology, Department of Biology ETH Zürich Zürich SwitzerlandInstitute of Microbiology, Department of Biology ETH Zürich Zürich SwitzerlandAbstract Introduction Epidemiological data suggest that persistent viral infections impair immune homeostasis and immune responsiveness. Previous studies showed that chronic virus infections negatively impact bystander T‐cell differentiation and memory formation but there is limited knowledge of how chronic virus infections impinge on heterologous naive T‐cell populations. Methods We used adoptive transfer of naive CD8 T cells with defined nonviral specificity into hosts, which were subsequently chronically infected with lymphocytic choriomeningitis virus, followed by analyses of numeric, phenotypic, and functional changes provoked in the chronically infected host. Results We demonstrate that chronic virus infections have a profound effect on the number and phenotype of naive bystander CD8 T cells. Moreover, primary expansion upon antigen encounter was severely compromised in chronically infected hosts. However, when naive bystander CD8 T cells were transferred from the chronically infected mice into naive hosts, they regained their expansion potential. Conversely, when chronically infected hosts were supplied with additional antigen‐presenting cells (APCs), primary expansion of the naive CD8 T cells was restored to levels of the uninfected hosts. Conclusions Our results document numeric, phenotypic, and functional adaptation of bystander naive CD8 T cells during nonrelated chronic viral infection. Their functional impairment was only evident in the chronically infected host, indicating that T‐cell extrinsic factors, in particular the quality of priming APCs, are responsible for the impaired function of naive bystander T cells in the chronically infected hosts.https://doi.org/10.1002/iid3.300CD8 T cellschronic virus infectionLCMVnaive bystander T cellsT‐cell primin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Isabel Barnstorf Suzanne P. M. Welten Mariana Borsa Nicolas S. Baumann Katharina Pallmer Nicole Joller Roman Spörri Annette Oxenius |
spellingShingle |
Isabel Barnstorf Suzanne P. M. Welten Mariana Borsa Nicolas S. Baumann Katharina Pallmer Nicole Joller Roman Spörri Annette Oxenius Chronic viral infections impinge on naive bystander CD8 T cells Immunity, Inflammation and Disease CD8 T cells chronic virus infection LCMV naive bystander T cells T‐cell primin |
author_facet |
Isabel Barnstorf Suzanne P. M. Welten Mariana Borsa Nicolas S. Baumann Katharina Pallmer Nicole Joller Roman Spörri Annette Oxenius |
author_sort |
Isabel Barnstorf |
title |
Chronic viral infections impinge on naive bystander CD8 T cells |
title_short |
Chronic viral infections impinge on naive bystander CD8 T cells |
title_full |
Chronic viral infections impinge on naive bystander CD8 T cells |
title_fullStr |
Chronic viral infections impinge on naive bystander CD8 T cells |
title_full_unstemmed |
Chronic viral infections impinge on naive bystander CD8 T cells |
title_sort |
chronic viral infections impinge on naive bystander cd8 t cells |
publisher |
Wiley |
series |
Immunity, Inflammation and Disease |
issn |
2050-4527 |
publishDate |
2020-09-01 |
description |
Abstract Introduction Epidemiological data suggest that persistent viral infections impair immune homeostasis and immune responsiveness. Previous studies showed that chronic virus infections negatively impact bystander T‐cell differentiation and memory formation but there is limited knowledge of how chronic virus infections impinge on heterologous naive T‐cell populations. Methods We used adoptive transfer of naive CD8 T cells with defined nonviral specificity into hosts, which were subsequently chronically infected with lymphocytic choriomeningitis virus, followed by analyses of numeric, phenotypic, and functional changes provoked in the chronically infected host. Results We demonstrate that chronic virus infections have a profound effect on the number and phenotype of naive bystander CD8 T cells. Moreover, primary expansion upon antigen encounter was severely compromised in chronically infected hosts. However, when naive bystander CD8 T cells were transferred from the chronically infected mice into naive hosts, they regained their expansion potential. Conversely, when chronically infected hosts were supplied with additional antigen‐presenting cells (APCs), primary expansion of the naive CD8 T cells was restored to levels of the uninfected hosts. Conclusions Our results document numeric, phenotypic, and functional adaptation of bystander naive CD8 T cells during nonrelated chronic viral infection. Their functional impairment was only evident in the chronically infected host, indicating that T‐cell extrinsic factors, in particular the quality of priming APCs, are responsible for the impaired function of naive bystander T cells in the chronically infected hosts. |
topic |
CD8 T cells chronic virus infection LCMV naive bystander T cells T‐cell primin |
url |
https://doi.org/10.1002/iid3.300 |
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