NDLI: Differential effector pathways regulate memory CD8 T-cell immunity against Plasmodium berghei versus Plasmodium yoelii sporozoites1

Content Provider	PubMed Central
Author	Butler, Noah S. Schmidt, Nathan W. Harty, John T.
Abstract	Malaria results in >1,000,000 deaths per year worldwide. Although no licensed vaccine yet exists, much effort is currently focused on subunit vaccines that elicit CD8 T cell responses directed against Plasmodium parasite liver stage antigens. Multiple immune-effector molecules play a role in anti-microbial immunity mediated by memory CD8 T cells including IFN-γ, perforin, TRAIL, FasL and TNF-α. However, it is not known which pathways are required for memory CD8 T cell-mediated immunity against liver stage Plasmodium infection. Here, 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 IFN-γ-dependent, while perforin was only involved in protection against P. yoelii. We further show that neutralization of TNF-α in immunized mice markedly reduces memory CD8 T cell-mediated protection against both parasite species. Thus, our studies identify both IFN-γ and TNF-α as important components of the non-cytolytic pathways that underlie memory CD8 T cell-mediated immunity against liver stage Plasmodium infection. Our studies also show that the effector pathways memory CD8 T cells utilize to eliminate liver stage infection are in part Plasmodium species-specific. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.
Related Links	http://dx.doi.org/10.4049/jimmunol.0903529
Ending Page	2538
Page Count	11
Starting Page	2528
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	5
Volume Number	184
Language	English
Publisher Date	2010-03-01
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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