Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection

Mitchell A Luangrath; Megan E Schmidt; Stacey M Hartwig; Steven M Varga

doi:10.4049/immunohorizons.2000067

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Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection

Journal article

Open access

Peer reviewed

Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection

Mitchell A Luangrath, Megan E Schmidt, Stacey M Hartwig and Steven M Varga

ImmunoHorizons, Vol.5(2), pp.59-69

02/03/2021

DOI: 10.4049/immunohorizons.2000067

PMCID: PMC8299542

PMID: 33536235

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Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young children. The T cell response plays a critical role in facilitating clearance of an acute RSV infection, and memory T cell responses are vital for protection against secondary RSV exposures. Tissue-resident memory (TRM) T cells have been identified as a subset of memory T cells that reside in nonlymphoid tissues and are critical for providing long-term immunity. There is currently limited information regarding the establishment and longevity of TRM T cell responses elicited following an acute RSV infection as well as their role in protection against repeated RSV infections. In this study, we examined the magnitude, phenotype, and protective capacity of TRM CD4 and CD8 T cells in the lungs of BALB/c mice following an acute RSV infection. TRM CD4 and CD8 T cells were established within the lungs and waned by 149 d following RSV infection. To determine the protective capacity of TRMs, FTY720 administration was used to prevent trafficking of peripheral memory T cells into the lungs prior to challenge of RSV-immune mice, with a recombinant influenza virus expressing either an RSV-derived CD4 or CD8 T cell epitope. We observed enhanced viral clearance in RSV-immune mice, suggesting that TRM CD8 T cells can contribute to protection against a secondary RSV infection. Given the protective capacity of TRMs, future RSV vaccine candidates should focus on the generation of these cell populations within the lung to induce effective immunity against RSV infection.

Animals

CD4-Positive T-Lymphocytes - immunology

CD8-Positive T-Lymphocytes - immunology

Epitopes, T-Lymphocyte - administration & dosage

Epitopes, T-Lymphocyte - genetics

Epitopes, T-Lymphocyte - immunology

Female

Fingolimod Hydrochloride - pharmacology

Immunologic Memory

Influenza Vaccines - administration & dosage

Influenza Vaccines - genetics

Influenza Vaccines - immunology

Lung - immunology

Lung - virology

Memory T Cells - drug effects

Memory T Cells - immunology

Mice

Mice, Inbred BALB C

Respiratory Syncytial Virus Infections - immunology

Respiratory Syncytial Virus Infections - prevention & control

Respiratory Syncytial Viruses - immunology

Vaccines, Synthetic - administration & dosage

Vaccines, Synthetic - immunology

Details

Title: Subtitle: Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection
Creators: Mitchell A Luangrath - University of Iowa
Megan E Schmidt - University of Iowa
Stacey M Hartwig - University of Iowa
Steven M Varga - University of Iowa
Resource Type: Journal article
Publication Details: ImmunoHorizons, Vol.5(2), pp.59-69
DOI: 10.4049/immunohorizons.2000067
PMID: 33536235
PMCID: PMC8299542
NLM abbreviation: Immunohorizons
ISSN: 2573-7732
eISSN: 2573-7732
Grant note: T32 AI007485 / NIAID NIH HHS R01 AI124093 / NIAID NIH HHS
Language: English
Date published: 02/03/2021
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Critical Care; Stead Family Department of Pediatrics; Pathology; Community and Behavioral Health
Record Identifier: 9984297436502771

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