A role for IFN-gamma from antigen-specific CD8+ T cells in protective immunity to Listeria monocytogenes

Kelly A N Messingham; Vladimir P Badovinac; Ali Jabbari; John T Harty

doi:10.4049/jimmunol.179.4.2457

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A role for IFN-gamma from antigen-specific CD8+ T cells in protective immunity to Listeria monocytogenes

Journal article

Peer reviewed

A role for IFN-gamma from antigen-specific CD8+ T cells in protective immunity to Listeria monocytogenes

Kelly A N Messingham, Vladimir P Badovinac, Ali Jabbari and John T Harty

The Journal of immunology (1950), Vol.179(4), pp.2457-2466

08/15/2007

DOI: 10.4049/jimmunol.179.4.2457

PMID: 17675507

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Abstract

Whether IFN-gamma contributes to the per-cell protective capacity of memory CD8(+) T cells against Listeria monocytogenes (LM) has not been formally tested. In this study, we generated LM Ag-specific memory CD8(+) T cells via immunization of wild-type (WT) and IFN-gamma-deficient (gamma knockout (GKO)) mice with LM peptide-coated dendritic cells and compared them phenotypically and functionally. Immunization of WT and GKO mice resulted in memory CD8(+) T cells that were similar in number, functional avidity, TCR repertoire use, and memory phenotype. The protective capacity of memory CD8(+) T cells from immunized WT and GKO mice was evaluated after adoptive transfer of equal numbers of WT or GKO cells into naive BALB/c mice followed by LM challenge. The adoptively transferred CD8(+) T cells from GKO donors exhibited a decreased ability to reduce bacterial numbers in the organs of recipient mice when compared with an equivalent number of Ag-matched WT CD8(+) T cells. This deficiency was most evident early (day 3) after infection if a relatively low infectious dose was used; however, transferring fewer memory CD8(+) T cells or increasing the LM challenge dose revealed a more pronounced defect in protective immunity mediated by the CD8(+) T cells from GKO mice. Our studies identified a decrease in Ag-specific target cell lysis in vivo by CD8(+) T cells from GKO mice as the mechanism for the decreased protective immunity after LM challenge. Further studies suggest that the lack of IFN-gamma production by the Ag-specific CD8 T cells themselves diminishes target cell sensitivity to cytolysis, thereby reducing the lytic potency of IFN-gamma-deficient LM-specific memory CD8(+) T cells.

Immunization

CD8-Positive T-Lymphocytes - microbiology

CD8-Positive T-Lymphocytes - pathology

Listeriosis - genetics

Dendritic Cells - immunology

Antigens, Bacterial - immunology

Dendritic Cells - pathology

Adoptive Transfer

Listeria monocytogenes - immunology

Mice, Knockout

Animals

Time Factors

Interferon-gamma - immunology

Listeriosis - immunology

Dendritic Cells - microbiology

Female

Mice

Mice, Inbred BALB C

CD8-Positive T-Lymphocytes - immunology

Interferon-gamma - deficiency

Immunologic Memory - genetics

Details

Title: Subtitle: A role for IFN-gamma from antigen-specific CD8+ T cells in protective immunity to Listeria monocytogenes
Creators: Kelly A N Messingham - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Vladimir P Badovinac
Ali Jabbari
John T Harty
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.179(4), pp.2457-2466
DOI: 10.4049/jimmunol.179.4.2457
PMID: 17675507
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI50073 / NIAID NIH HHS AI46653 / NIAID NIH HHS AI59752 / NIAID NIH HHS AAI42767 / PHS HHS
Language: English
Date published: 08/15/2007
Academic Unit: Dermatology; Microbiology and Immunology; Pathology
Record Identifier: 9984025677202771

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