Cargando…
Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection
The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza B (B/Brisbane/60/2008)...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875387/ https://www.ncbi.nlm.nih.gov/pubmed/35215193 http://dx.doi.org/10.3390/pathogens11020251 |
_version_ | 1784657900352831488 |
---|---|
author | Rattan, Ajitanuj White, Chantelle L. Nelson, Sean Eismann, Max Padilla-Quirarte, Herbey Glover, Maryah A. Dileepan, Thamotharampillai Marathe, Bindumadhav M. Govorkova, Elena A. Webby, Richard J. Richards, Katherine A. Sant, Andrea J. |
author_facet | Rattan, Ajitanuj White, Chantelle L. Nelson, Sean Eismann, Max Padilla-Quirarte, Herbey Glover, Maryah A. Dileepan, Thamotharampillai Marathe, Bindumadhav M. Govorkova, Elena A. Webby, Richard J. Richards, Katherine A. Sant, Andrea J. |
author_sort | Rattan, Ajitanuj |
collection | PubMed |
description | The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza B (B/Brisbane/60/2008) virus and, using an iterative peptide discovery strategy, have identified a series of robustly elicited individual CD4 T cell peptide specificities. The CD4 T cell repertoire encompassed at least eleven major epitopes distributed across hemagglutinin, nucleoprotein, neuraminidase, and non-structural protein 1 and are readily detected in the draining lymph node, spleen, and lung. Within the lung, the CD4 T cells are localized to both lung vasculature and tissue but are highly enriched in the lung tissue after infection. When studied by flow cytometry and MHC class II: peptide tetramers, CD4 T cells express prototypical markers of tissue residency including CD69, CD103, and high surface levels of CD11a. Collectively, our studies will enable more sophisticated analyses of influenza B virus infection, where the fate and function of the influenza B-specific CD4 T cells elicited by infection and vaccination can be studied as well as the impact of anti-viral reagents and candidate vaccines on the abundance, functionality, and localization of the elicited CD4 T cells. |
format | Online Article Text |
id | pubmed-8875387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88753872022-02-26 Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection Rattan, Ajitanuj White, Chantelle L. Nelson, Sean Eismann, Max Padilla-Quirarte, Herbey Glover, Maryah A. Dileepan, Thamotharampillai Marathe, Bindumadhav M. Govorkova, Elena A. Webby, Richard J. Richards, Katherine A. Sant, Andrea J. Pathogens Article The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza B (B/Brisbane/60/2008) virus and, using an iterative peptide discovery strategy, have identified a series of robustly elicited individual CD4 T cell peptide specificities. The CD4 T cell repertoire encompassed at least eleven major epitopes distributed across hemagglutinin, nucleoprotein, neuraminidase, and non-structural protein 1 and are readily detected in the draining lymph node, spleen, and lung. Within the lung, the CD4 T cells are localized to both lung vasculature and tissue but are highly enriched in the lung tissue after infection. When studied by flow cytometry and MHC class II: peptide tetramers, CD4 T cells express prototypical markers of tissue residency including CD69, CD103, and high surface levels of CD11a. Collectively, our studies will enable more sophisticated analyses of influenza B virus infection, where the fate and function of the influenza B-specific CD4 T cells elicited by infection and vaccination can be studied as well as the impact of anti-viral reagents and candidate vaccines on the abundance, functionality, and localization of the elicited CD4 T cells. MDPI 2022-02-15 /pmc/articles/PMC8875387/ /pubmed/35215193 http://dx.doi.org/10.3390/pathogens11020251 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rattan, Ajitanuj White, Chantelle L. Nelson, Sean Eismann, Max Padilla-Quirarte, Herbey Glover, Maryah A. Dileepan, Thamotharampillai Marathe, Bindumadhav M. Govorkova, Elena A. Webby, Richard J. Richards, Katherine A. Sant, Andrea J. Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection |
title | Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection |
title_full | Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection |
title_fullStr | Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection |
title_full_unstemmed | Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection |
title_short | Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection |
title_sort | development of a mouse model to explore cd4 t cell specificity, phenotype, and recruitment to the lung after influenza b infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875387/ https://www.ncbi.nlm.nih.gov/pubmed/35215193 http://dx.doi.org/10.3390/pathogens11020251 |
work_keys_str_mv | AT rattanajitanuj developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT whitechantellel developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT nelsonsean developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT eismannmax developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT padillaquirarteherbey developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT glovermaryaha developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT dileepanthamotharampillai developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT marathebindumadhavm developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT govorkovaelenaa developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT webbyrichardj developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT richardskatherinea developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection AT santandreaj developmentofamousemodeltoexplorecd4tcellspecificityphenotypeandrecruitmenttothelungafterinfluenzabinfection |