Differential effector pathways regulate memory CD8 T cell immunity against Plasmodium berghei versus P. yoelii sporozoites

Noah S Butler; Nathan W Schmidt; John T Harty

doi:10.4049/jimmunol.0903529

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Differential effector pathways regulate memory CD8 T cell immunity against Plasmodium berghei versus P. yoelii sporozoites

Journal article

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Peer reviewed

Differential effector pathways regulate memory CD8 T cell immunity against Plasmodium berghei versus P. yoelii sporozoites

Noah S Butler, Nathan W Schmidt and John T Harty

The Journal of immunology (1950), Vol.184(5), pp.2528-2538

03/01/2010

DOI: 10.4049/jimmunol.0903529

PMCID: PMC2904689

PMID: 20097864

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Abstract

Malaria results in >1,000,000 deaths per year worldwide. Although no licensed vaccine exists, much effort is currently focused on subunit vaccines that elicit CD8 T cell responses directed against Plasmodium parasite liver stage Ags. Multiple immune-effector molecules play a role in antimicrobial immunity mediated by memory CD8 T cells, including IFN-gamma, perforin, TRAIL, Fas ligand, and TNF-alpha. However, it is not known which pathways are required for memory CD8 T cell-mediated immunity against liver stage Plasmodium infection. In this study, we used a novel immunization strategy to generate memory CD8 T cells in the BALB/c mouse model of P. berghei or P. yoelii sporozoite infection to examine the role of immune-effector molecules in resistance to the liver stage infection. Our studies reveal that endogenous memory CD8 T cell-mediated protection against both parasite species is, in part, dependent on IFN-gamma, whereas perforin was only critical in protection against P. yoelii. We further show that neutralization of TNF-alpha in immunized mice markedly reduces memory CD8 T cell-mediated protection against both parasite species. Thus, our studies identify IFN-gamma and TNF-alpha as important components of the noncytolytic pathways that underlie memory CD8 T cell-mediated immunity against liver stage Plasmodium infection. Our studies also show that the effector pathways that memory CD8 T cells use to eliminate liver stage infection are, in part, Plasmodium species specific.

Tumor Necrosis Factor-alpha - metabolism

Plasmodium berghei - immunology

Fas Ligand Protein - metabolism

Perforin - genetics

Dendritic Cells - immunology

Liver Diseases, Parasitic - immunology

Listeria monocytogenes - immunology

Sporozoites - immunology

Fas Ligand Protein - immunology

Signal Transduction - immunology

Malaria Vaccines - immunology

TNF-Related Apoptosis-Inducing Ligand - deficiency

Tumor Necrosis Factor-alpha - immunology

CD8-Positive T-Lymphocytes - metabolism

Female

Perforin - immunology

Interferon-gamma - genetics

Interferon-gamma - deficiency

Dendritic Cells - metabolism

Immunologic Memory - immunology

Malaria - immunology

Plasmodium yoelii - immunology

TNF-Related Apoptosis-Inducing Ligand - immunology

Liver Diseases, Parasitic - parasitology

Mice, Knockout

Malaria - prevention & control

Perforin - deficiency

Animals

Malaria Vaccines - administration & dosage

Interferon-gamma - immunology

Malaria - parasitology

Culicidae - parasitology

Mice

Mice, Inbred BALB C

CD8-Positive T-Lymphocytes - immunology

TNF-Related Apoptosis-Inducing Ligand - genetics

Details

Title: Subtitle: Differential effector pathways regulate memory CD8 T cell immunity against Plasmodium berghei versus P. yoelii sporozoites
Creators: Noah S Butler - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Nathan W Schmidt
John T Harty
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.184(5), pp.2528-2538
DOI: 10.4049/jimmunol.0903529
PMID: 20097864
PMCID: PMC2904689
NLM abbreviation: J Immunol
ISSN: 1550-6606
eISSN: 1550-6606
Publisher: United States
Grant note: R01 AI085515-01A1 / NIAID NIH HHS R01 AI085515 / NIAID NIH HHS T32 AI0726024 / NIAID NIH HHS
Language: English
Date published: 03/01/2010
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984001161902771

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