IL-12 and NK Cells Are Required for Antigen-Specific Adaptive Immunity Against Malaria Initiated by CD8+ T Cells in the Plasmodium yoelii Model
Open accessAbstract
CD8+ T cells have been implicated as critical effector cells in protection against preerythrocytic stage malaria, including the potent protective immunity of mice and humans induced by immunization with radiation-attenuated Plasmodium spp. sporozoites. This immunity is directed against the Plasmodium spp. parasite developing within the host hepatocyte and for a number of years has been presumed to be mediated directly by CD8+ CTL or indirectly by IFN-γ released from CD8+ T cells. In this paper, in BALB/c mice, we establish that after immunization with irradiated sporozoites or DNA vaccines parasite-specific CD8+ T cells trigger a novel mechanism of adaptive immunity that is dependent on T cell- and non-T cell-derived cytokines, in particular IFN-γ and IL-12, and requires NK cells but not CD4+ T cells. The absolute requirement for CD8+ T cells to initiate such an effector mechanism, and the requirement for IL-12 and NK cells in such vaccine-induced protective immunity, are unique and underscore the complexity of the immune responses that protect against malaria and other intracellular pathogens.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The PSMD7 gene plays a critical role in the development of adaptive immunity or tolerance.
“This gene plays a critical role in the development of adaptive immunity or tolerance (Doolan and Hoffman, 1999).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Doolan and Hoffman, 1999
The section “IL-12 is required for P. yoelii sporozoite-induced protective immunity” (page not provided) assigns a critical role in the adaptive response to IL-12, not PSMD7. Searches for PSMD7 and immune tolerance found no passage in our copy addressing a role for that gene. (LLM, conf=0.77)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 7
- Hoffman, S. L., E. D. Franke, M. R. Hollingdale, and P. Druilhe. 1996. Attacking the infected hepatocyte. In Malaria Vaccine Development: A Multi-Immune Re- sponse Approach. S. L. Hoffman, ed. ASM Press, Washington, DC, pp. 35.
- Sedegah, M., R. Hedstrom, P. Hobart, and S. L. Hoffman. 1994. Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc. Natl. Acad. Sci. USA 91:9866.
- Weiss, W. R., M. Sedegah, R. L. Beaudoin, L. H. Miller, and M. F. Good. 1988. CD8 ϩ T cells (cytotoxic/suppressors) are required for protection in mice immu- nized with malaria sporozoites. Proc. Natl. Acad. Sci. USA 85:573.
- Renia, L., M. S. Marussig, D. Grillot, S. Pied, G. Corradin, F. Miltgen, G. Del Giudice, and D. Mazier. 1991. In vitro activity of CD4 ϩ and CD8 ϩ T lymphocytes from mice immunized with a synthetic malaria peptide. Proc. Natl. Acad. Sci. USA 88:7963.
- Yang Y., J. B. Waters, K. Fruh, and P. A. Peterson. 1992. Proteasomes are regulated by interferon ␥: implications for antigen processing. Proc. Natl. Acad. Sci. USA 89:4928.
- Geller, D. A., A. K. Nussler, M. Di Silvio, C. J. Lowenstein, R. A. Shapiro, S. C. Wang, R. L. Simmons, and T. R. Billiar. 1993. Cytokines, endotoxin, and glucocorticoids regulate the expression of inducible nitric oxide synthase in hepa- tocytes. Proc. Natl. Acad. Sci. USA 90:522.
- Sedegah, M., F. Finkelman, and S. L. Hoffman. 1994. Interleukin-12 induction of interferon-␥-dependent protection against malaria. Proc. Natl. Acad. Sci. USA 91:10700.
Cited by
Sorted by citations
Mekonnen, Y. A., Gültas, M., Effa, K., Hanotte, O., & Schmitt, A. O. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.01095 · Cited by 37 · see citing works
“This gene plays a critical role in the development of adaptive immunity or tolerance (Doolan and Hoffman, 1999).”
Background
- Authors
- Doolan, D. L., & Hoffman, S. L.
- Affiliations
- World Health Organization Regional Office for the Americas (US)
- Naval Medical Research Command (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-07
- Volume
- 163
- Issue
- 2
- Pages
- 884-892
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1588145372
- Cited by
- 183
- References
- 0
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 1 · 2015: 8 · 2014: 7 · 2013: 9 · 2012: 7
- FWCI
- 17.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Navy
- U.S. Army Medical Research and Development Command
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-12, natural killer cells, CD8+ T cells, malaria, Plasmodium yoelii, sporozoite immunization, radiation-attenuated sporozoites, DNA vaccine, interferon-gamma, adaptive immunity, protective immunity, hepatocyte infection, cytokines
- MeSH terms
- Animals, Antigens, Protozoan, Disease Models, Animal, Female, Immunity, Cellular, Interferon-gamma, Killer Cells, Natural, Malaria, Mice, Inbred BALB C, Nitric Oxide, Plasmodium yoelii, T-Lymphocytes, Cytotoxic, CD4-Positive T-Lymphocytes, Malaria Vaccines, Mice, Knockout, CD8-Positive T-Lymphocytes, Interleukin-12, Epitopes, T-Lymphocyte, Vaccines, DNA, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
