Perforin plays an unexpected role in regulating T-cell contraction during prolonged Listeria monocytogenes infection

Nathan W Schmidt; Aaruni Khanolkar; Lisa Hancox; Jonathan W Heusel; John T Harty

doi:10.1002/eji.201141902

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Perforin plays an unexpected role in regulating T-cell contraction during prolonged Listeria monocytogenes infection

Journal article

Peer reviewed

Perforin plays an unexpected role in regulating T-cell contraction during prolonged Listeria monocytogenes infection

Nathan W Schmidt, Aaruni Khanolkar, Lisa Hancox, Jonathan W Heusel and John T Harty

European journal of immunology, Vol.42(3), pp.629-640

03/2012

DOI: 10.1002/eji.201141902

PMCID: PMC3418886

PMID: 22161269

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Abstract

After infection or vaccination, antigen-specific T cells proliferate then contract in numbers to a memory set point. T-cell contraction is observed after both acute and prolonged infections although it is unknown if contraction is regulated similarly in both scenarios. Here, we show that contraction of antigen-specific CD8(+) and CD4(+) T cells is markedly reduced in TNF/perforin-double deficient (DKO) mice responding to attenuated Listeria monocytogenes infection. Reduced contraction in DKO mice was associated with delayed clearance of infection and sustained T-cell proliferation during the normal contraction interval. Mechanistically, sustained T-cell proliferation mapped to prolonged infection in the absence of TNF; however, reduced contraction required the additional absence of perforin since T cells in mice lacking either TNF or perforin (singly deficient) underwent normal contraction. Thus, while T-cell contraction after acute infection is independent of peforin, a perforin-dependent pathway plays a previously unappreciated role to mediate contraction of antigen-specific CD8(+) and CD4(+) T cells during prolonged L. monocytogenes infection.

CD4-Positive T-Lymphocytes - microbiology

CD8-Positive T-Lymphocytes - microbiology

Cell Proliferation

Specific Pathogen-Free Organisms

Mice, Inbred C57BL

Listeria monocytogenes - immunology

Mice, Knockout

CD4-Positive T-Lymphocytes - immunology

Animals

Flow Cytometry

Listeriosis - immunology

Tumor Necrosis Factor-alpha - immunology

Listeriosis - microbiology

Mice

Perforin - immunology

CD8-Positive T-Lymphocytes - immunology

Immunologic Memory - immunology

Details

Title: Subtitle: Perforin plays an unexpected role in regulating T-cell contraction during prolonged Listeria monocytogenes infection
Creators: Nathan W Schmidt - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Aaruni Khanolkar
Lisa Hancox
Jonathan W Heusel
John T Harty
Resource Type: Journal article
Publication Details: European journal of immunology, Vol.42(3), pp.629-640
DOI: 10.1002/eji.201141902
PMID: 22161269
PMCID: PMC3418886
NLM abbreviation: Eur J Immunol
ISSN: 0014-2980
eISSN: 1521-4141
Publisher: Germany
Grant note: AI59792 / NIAID NIH HHS R37 AI042767 / NIAID NIH HHS 1 F32 AI084329-01 / NIAID NIH HHS R01 AI046653 / NIAID NIH HHS F32 AI084329 / NIAID NIH HHS AI42767 / NIAID NIH HHS R01 AI042767 / NIAID NIH HHS AI46653 / NIAID NIH HHS
Language: English
Date published: 03/2012
Academic Unit: Pathology
Record Identifier: 9984047888102771

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