The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection
Tissue-resident memory T cells (TRM) reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG) most-effectively induces CD8+ and CD4+ TRM cells against murine cytomegalovirus (MCMV), which persists in and spreads from this organ. TRM genera...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2015-11-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715011365 |
id |
doaj-9e1ebcc7bbe94fa6aaede259221a4ff3 |
---|---|
record_format |
Article |
spelling |
doaj-9e1ebcc7bbe94fa6aaede259221a4ff32020-11-24T20:40:16ZengElsevierCell Reports2211-12472015-11-011361125113610.1016/j.celrep.2015.09.082The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus InfectionJenny Tosca Thom0Thomas Christian Weber1Senta Maria Walton2Nicole Torti3Annette Oxenius4Institute of Microbiology, ETH Zürich, 8093 Zürich, SwitzerlandInstitute of Microbiology, ETH Zürich, 8093 Zürich, SwitzerlandInstitute of Microbiology, ETH Zürich, 8093 Zürich, SwitzerlandInstitute of Microbiology, ETH Zürich, 8093 Zürich, SwitzerlandInstitute of Microbiology, ETH Zürich, 8093 Zürich, SwitzerlandTissue-resident memory T cells (TRM) reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG) most-effectively induces CD8+ and CD4+ TRM cells against murine cytomegalovirus (MCMV), which persists in and spreads from this organ. TRM generation depended on local antigen for CD4+, but not CD8+, TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8+ T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8+ T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8+ T cells in protecting mucosal tissues against CMV infection.http://www.sciencedirect.com/science/article/pii/S2211124715011365 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jenny Tosca Thom Thomas Christian Weber Senta Maria Walton Nicole Torti Annette Oxenius |
spellingShingle |
Jenny Tosca Thom Thomas Christian Weber Senta Maria Walton Nicole Torti Annette Oxenius The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection Cell Reports |
author_facet |
Jenny Tosca Thom Thomas Christian Weber Senta Maria Walton Nicole Torti Annette Oxenius |
author_sort |
Jenny Tosca Thom |
title |
The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection |
title_short |
The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection |
title_full |
The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection |
title_fullStr |
The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection |
title_full_unstemmed |
The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection |
title_sort |
salivary gland acts as a sink for tissue-resident memory cd8+ t cells, facilitating protection from local cytomegalovirus infection |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2015-11-01 |
description |
Tissue-resident memory T cells (TRM) reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG) most-effectively induces CD8+ and CD4+ TRM cells against murine cytomegalovirus (MCMV), which persists in and spreads from this organ. TRM generation depended on local antigen for CD4+, but not CD8+, TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8+ T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8+ T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8+ T cells in protecting mucosal tissues against CMV infection. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124715011365 |
work_keys_str_mv |
AT jennytoscathom thesalivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection AT thomaschristianweber thesalivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection AT sentamariawalton thesalivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection AT nicoletorti thesalivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection AT annetteoxenius thesalivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection AT jennytoscathom salivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection AT thomaschristianweber salivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection AT sentamariawalton salivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection AT nicoletorti salivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection AT annetteoxenius salivaryglandactsasasinkfortissueresidentmemorycd8tcellsfacilitatingprotectionfromlocalcytomegalovirusinfection |
_version_ |
1716827592865087488 |