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Cell Rep. 2016 Aug 16;16(7):1800-9. doi: 10.1016/j.celrep.2016.07.037. Epub 2016 Aug 4.

A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection.

Author information

1
Department of Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
2
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
3
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
5
Vanderbilt Technologies for Advanced Genomics Analyses and Research Design, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
6
Vanderbilt Technologies for Advanced Genomics Analyses and Research Design, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
7
Department of Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: sebastian.joyce@vanderbilt.edu.

Abstract

The nature and anatomic location of the protective memory CD8(+) T cell subset induced by intranasal vaccination remain poorly understood. We developed a vaccination model to assess the anatomic location of protective memory CD8(+) T cells and their role in lower airway infections. Memory CD8(+) T cells elicited by local intranasal, but not systemic, vaccination with an engineered non-replicative CD8(+) T cell-targeted antigen confer enhanced protection to a lethal respiratory viral challenge. This protection depends on a distinct CXCR3(LO) resident memory CD8(+) T (Trm) cell population that preferentially localizes to the pulmonary interstitium. Because they are positioned close to the mucosa, where infection occurs, interstitial Trm cells act before inflammation can recruit circulating memory CD8(+) T cells into the lung tissue. This results in a local protective immune response as early as 1 day post-infection. Hence, vaccine strategies that induce lung interstitial Trm cells may confer better protection against respiratory pathogens.

PMID:
27498869
PMCID:
PMC5021515
DOI:
10.1016/j.celrep.2016.07.037
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

All authors have declared that no conflict of interest exists.

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