| Differential effector pathways regulate memory CD8 T cell immunity against Plasmodium berghei versus P. yoelii sporozoites. | |
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MedLine Citation:
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PMID: 20097864 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Noah S Butler; Nathan W Schmidt; John T Harty |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-01-22 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 184 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-18 Completed Date: 2010-05-04 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 2528-38 Citation Subset: AIM; IM |
Affiliation:
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Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals CD8-Positive T-Lymphocytes / immunology*, metabolism Culicidae / parasitology Dendritic Cells / immunology, metabolism Fas Ligand Protein / immunology, metabolism Female Immunologic Memory / immunology Interferon-gamma / deficiency, genetics, immunology Listeria monocytogenes / immunology Liver Diseases, Parasitic / immunology, parasitology Malaria / immunology*, parasitology, prevention & control Malaria Vaccines / administration & dosage, immunology* Mice Mice, Inbred BALB C Mice, Knockout Perforin / deficiency, genetics, immunology Plasmodium berghei / immunology* Plasmodium yoelii / immunology* Signal Transduction / immunology Sporozoites / immunology* TNF-Related Apoptosis-Inducing Ligand / deficiency, genetics, immunology Tumor Necrosis Factor-alpha / immunology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI085515-01A1/AI/NIAID NIH HHS; R01 AI085515-02/AI/NIAID NIH HHS; T32 AI0726024/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fas Ligand Protein; 0/Fasl protein, mouse; 0/Malaria Vaccines; 0/TNF-Related Apoptosis-Inducing Ligand; 0/Tnfsf10 protein, mouse; 0/Tumor Necrosis Factor-alpha; 126465-35-8/Perforin; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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