Perforin-deficient CD8+ T cells: in vivo priming and antigen-specific immunity against Listeria monocytogenes

Douglas W White; Adam MacNeil; Dirk H Busch; Ingrid M Pilip; Eric G Pamer; John T Harty

doi:10.4049/jimmunol.162.2.980

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Perforin-deficient CD8+ T cells: in vivo priming and antigen-specific immunity against Listeria monocytogenes

Journal article

Peer reviewed

Perforin-deficient CD8+ T cells: in vivo priming and antigen-specific immunity against Listeria monocytogenes

Douglas W White, Adam MacNeil, Dirk H Busch, Ingrid M Pilip, Eric G Pamer and John T Harty

The Journal of immunology (1950), Vol.162(2), pp.980-988

01/15/1999

DOI: 10.4049/jimmunol.162.2.980

PMID: 9916723

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Abstract

CD8+ T cells require perforin to mediate immunity against some, but not all, intracellular pathogens. Previous studies with H-2b MHC perforin gene knockout (PO) mice revealed both perforin-dependent and perforin-independent pathways of CD8+ T cell-mediated immunity to Listeria monocytogenes (LM). In this study, we address two previously unresolved issues regarding the requirement for perforin in antilisterial immunity: 1) Is CD8+ T cell-mediated, perforin-independent immunity specific for a single Ag or generalizable to multiple Ags? 2) Is there a deficiency in the priming of the CD8+ T cell compartment of PO mice following an immunizing challenge with LM? We used H-2d MHC PO mice to generate CD8+ T cell lines individually specific for three known Ags expressed by a recombinant strain of virulent LM. Adoptive transfer experiments into BALB/c host mice revealed that immunity can be mediated by PO CD8+ T cells specific for all Ags examined, indicating that perforin-independent immunity is not limited to CD8+ T cells that recognize listeriolysin O. Analysis of epitope-specific CD8+ T cell expansion by MHC class I tetramer staining and ELISPOT revealed no deficiency in either the primary or secondary response to LM infection in PO mice. These results demonstrate that the perforin-independent pathway of antilisterial resistance mediated by CD8+ T cells is generalizable to multiple epitopes. Furthermore, the results show that reduced antilisterial resistance observed with polyclonal PO CD8+ T cells is a consequence of a deficiency in effector function and not a result of suboptimal CD8+ T cell priming.

T-Lymphocyte Subsets - immunology

Spleen - immunology

Peptides - genetics

Histocompatibility Antigen H-2D

Listeria monocytogenes - immunology

Antigens, Bacterial - biosynthesis

Antigens, Bacterial - genetics

H-2 Antigens - genetics

Recombination, Genetic

Listeriosis - immunology

CD8-Positive T-Lymphocytes - metabolism

Pore Forming Cytotoxic Proteins

Epitopes, T-Lymphocyte - immunology

Perforin

Cell Line

Lymphocyte Activation

Peptides - immunology

Spleen - cytology

Immunity, Innate

Membrane Glycoproteins - genetics

Mice, Knockout

Animals

T-Lymphocyte Subsets - metabolism

Listeria monocytogenes - genetics

Mice

Mice, Inbred BALB C

CD8-Positive T-Lymphocytes - immunology

Membrane Glycoproteins - deficiency

Details

Title: Subtitle: Perforin-deficient CD8+ T cells: in vivo priming and antigen-specific immunity against Listeria monocytogenes
Creators: Douglas W White - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City 52242, USA
Adam MacNeil
Dirk H Busch
Ingrid M Pilip
Eric G Pamer
John T Harty
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.162(2), pp.980-988
DOI: 10.4049/jimmunol.162.2.980
PMID: 9916723
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI42767 / NIAID NIH HHS AI36864 / NIAID NIH HHS
Language: English
Date published: 01/15/1999
Academic Unit: Pathology
Record Identifier: 9984046921002771

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