Antigen-dependent and -independent contributions to primary memory CD8 T cell activation and protection following infection

Matthew D Martin; Vladimir P Badovinac

doi:10.1038/srep18022

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Antigen-dependent and -independent contributions to primary memory CD8 T cell activation and protection following infection

Journal article

Open access

Peer reviewed

Antigen-dependent and -independent contributions to primary memory CD8 T cell activation and protection following infection

Matthew D Martin and Vladimir P Badovinac

Scientific reports, Vol.5(1), pp.18022-18022

12/10/2015

DOI: 10.1038/srep18022

PMCID: PMC4675085

PMID: 26658291

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https://doi.org/10.1038/srep18022View

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Abstract

Memory CD8 T-cell activation, including expression of IFN-γ and granzymeB, can be induced by antigen (Ag)-dependent signals through the T-cell-receptor, or by pathogen-derived inflammatory cytokines in an Ag-independent manner. Recent studies have come to conflicting results regarding the contributions of Ag and/or inflammation to memory CD8 T-cell activation. Additionally, research has indicated that inflammation-driven CD8 T-cell responses during un-related infections (bystander activation) have the potential to provide protection, but whether protection occurs in immuno-competent hosts is unclear. To investigate these questions, we examined activation of virus-specific memory CD8 T-cells following infection with L. monocytogenes either expressing or not cognate Ag. We show that Ag and inflammation act synergistically in vitro to induce memory activation. In vivo, we found that when memory CD8 T-cells significantly contribute to clearance of infection, early activation and continued responses by these cells are enhanced by cognate Ag recognition. Mechanistically, we show that bystander responses by memory are dependent upon the dose of infection and the amount of inflammation elicited following infection and are able to provide protection in IFN-γ deficient mice, but not in immuno-competent hosts. The data elucidate the requirements for memory CD8 T-cell activation and the protective role of bystander responses.

Inflammation - microbiology

Mice, Inbred C57BL

Inflammation - immunology

Listeria monocytogenes - immunology

Mice, Knockout

Lymphocyte Activation - immunology

Animals

Interferon-gamma - immunology

Listeriosis - immunology

Antigens - immunology

Mice

CD8-Positive T-Lymphocytes - immunology

Immunologic Memory - immunology

Cytokines - immunology

Details

Title: Subtitle: Antigen-dependent and -independent contributions to primary memory CD8 T cell activation and protection following infection
Creators: Matthew D Martin - Department of Pathology, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Vladimir P Badovinac - Department of Pathology, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.5(1), pp.18022-18022
DOI: 10.1038/srep18022
PMID: 26658291
PMCID: PMC4675085
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: R01 AI114543 / NIAID NIH HHS AI119160 / NIAID NIH HHS R21 AI119160 / NIAID NIH HHS GM113961 / NIGMS NIH HHS T32 AI007485 / NIAID NIH HHS R01 GM113961 / NIGMS NIH HHS T32AI007485 / NIAID NIH HHS AI114543 / NIAID NIH HHS
Language: English
Date published: 12/10/2015
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984046832402771

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