Journal article
Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity
Science immunology, Vol.2(7), p.eaag2031
01/06/2017
DOI: 10.1126/sciimmunol.aag2031
PMCID: PMC5590757
PMID: 28783666
Abstract
Lung-resident memory CD8 T cells (T
) induced by influenza A virus (IAV) that are pivotal for providing subtype-transcending protection against IAV infection (heterosubtypic immunity) are not maintained long term, causing gradual loss of protection. The short-lived nature of lung T
contrasts sharply with long-term maintenance of T
induced by localized infections in the skin and in other tissues. We show that the decline in lung T
is determined by an imbalance between apoptosis and lung recruitment and conversion to T
of circulating memory cells. We show that circulating effector memory cells (T
) rather than central memory cells (T
) are the precursors for conversion to lung T
Time-dependent changes in expression of genes critical for lymphocyte trafficking and T
differentiation, in concert with enrichment of T
, diminish the capacity of circulating memory CD8 T cells to form T
with time, explaining why IAV-induced T
are not stably maintained. Systemic booster immunization, through increasing the number of circulating T
, increases lung T
, providing a potential new avenue to enhance IAV vaccines.
Details
- Title: Subtitle
- Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity
- Creators
- Bram Slütter - Cluster of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, NetherlandsNatalija Van Braeckel-Budimir - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USAGeorges Abboud - Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32611, USASteven M Varga - Department of Pathology, University of Iowa, Iowa City, IA 52242, USAShahram Salek-Ardakani - Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32611, USAJohn T Harty - Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Science immunology, Vol.2(7), p.eaag2031
- DOI
- 10.1126/sciimmunol.aag2031
- PMID
- 28783666
- PMCID
- PMC5590757
- NLM abbreviation
- Sci Immunol
- ISSN
- 2470-9468
- eISSN
- 2470-9468
- Publisher
- United States
- Grant note
- R01 AI114543 / NIAID NIH HHS R01 AI042767 / NIAID NIH HHS R37 AI042767 / NIAID NIH HHS R21 AI042767 / NIAID NIH HHS
- Language
- English
- Date published
- 01/06/2017
- Academic Unit
- Graduate College Admin and Gen; Microbiology and Immunology; Pathology
- Record Identifier
- 9984047743202771
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