Deficient anti-listerial immunity in the absence of perforin can be restored by increasing memory CD8+ T cell numbers

Kelly A Nordyke Messingham; Vladimir P Badovinac; John T Harty

doi:10.4049/jimmunol.171.8.4254

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Deficient anti-listerial immunity in the absence of perforin can be restored by increasing memory CD8+ T cell numbers

Journal article

Open access

Peer reviewed

Deficient anti-listerial immunity in the absence of perforin can be restored by increasing memory CD8+ T cell numbers

Kelly A Nordyke Messingham, Vladimir P Badovinac and John T Harty

The Journal of immunology (1950), Vol.171(8), pp.4254-4262

10/15/2003

DOI: 10.4049/jimmunol.171.8.4254

PMID: 14530349

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Abstract

Compared with wild-type (WT) mice, Listeria monocytogenes (LM)-vaccinated perforin-deficient (PKO) mice have elevated levels of CD8(+) T cell memory, but exhibit reduced levels of protection against virulent LM. In this study, Ag-specific CD8(+) T cells from LM-vaccinated WT and PKO mice were used in adoptive transfer assays to determine the contribution of perforin-dependent cytolysis in protective immunity to LM. Perforin deficiency resulted in an approximately 5-fold reduction in the per-cell protective capacity of Ag-specific memory CD8(+) T cells that was not caused by differences in memory cell quality as measured by CD62L/CD27 expression, TCR repertoire use, functional avidity, differences in expansion of Ag-specific cells upon infection, or maintenance of memory levels over time. However, perforin-deficient CD8(+) T cells exhibited reduced in vivo cytotoxic function compared to WT CD8(+) T cells. Consistent with the existence of perforin-independent effector pathways, double-vaccinated PKO mice were as resistant to challenge with LM as single-vaccinated WT mice. Thus, increasing the number of memory CD8(+) T cells can overcome diminished per-cell protective immunity in the absence of perforin.

CD8-Positive T-Lymphocytes - cytology

CD8-Positive T-Lymphocytes - transplantation

Immunity, Innate - genetics

Adoptive Transfer

Listeria monocytogenes - immunology

Listeriosis - prevention & control

Membrane Glycoproteins - physiology

Immunization, Secondary

Listeriosis - immunology

Female

Immunization Schedule

Pore Forming Cytotoxic Proteins

Epitopes, T-Lymphocyte - immunology

Perforin

Immunologic Memory - genetics

Cytotoxicity, Immunologic - genetics

CD8-Positive T-Lymphocytes - microbiology

Listeriosis - genetics

Up-Regulation - genetics

Down-Regulation - genetics

Membrane Glycoproteins - genetics

Mice, Knockout

Animals

Bacterial Vaccines - administration & dosage

Bacterial Vaccines - immunology

Up-Regulation - immunology

Down-Regulation - immunology

Lymphocyte Count

Mice

Mice, Inbred BALB C

CD8-Positive T-Lymphocytes - immunology

Membrane Glycoproteins - deficiency

Details

Title: Subtitle: Deficient anti-listerial immunity in the absence of perforin can be restored by increasing memory CD8+ T cell numbers
Creators: Kelly A Nordyke Messingham - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Vladimir P Badovinac
John T Harty
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.171(8), pp.4254-4262
Publisher: United States
DOI: 10.4049/jimmunol.171.8.4254
PMID: 14530349
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: AI42767 / NIAID NIH HHS AI50073 / NIAID NIH HHS T32 A107260 / PHS HHS AI46653 / NIAID NIH HHS
Language: English
Date published: 10/15/2003
Academic Unit: Dermatology; Microbiology and Immunology; Pathology
Record Identifier: 9984047896402771

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