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Cited by 835

The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.

Interleukin 12 is required for the T-lymphocyte-independent induction of interferon gamma by an intracellular parasite and induces resistance in T-cell-deficient hosts.

Open access
Gazzinelli, R T, Hieny, S, Wynn, T A, Wolf, S, Sher, A·1993·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.90.13.6115
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Abstract

Immunity against the intracellular protozoan Toxoplasma gondii is highly dependent on interferon gamma (IFN-gamma). We have previously shown that, in addition to T lymphocytes, natural killer (NK) cells can be stimulated by the parasite to produce this cytokine by a reaction requiring adherent accessory cells and tumor necrosis factor alpha. We now demonstrate that a recently characterized cytokine, interleukin 12 (IL-12), is also necessary for parasite-induced IFN-gamma synthesis by NK cells. Anti-IL-12 antibodies completely inhibited T. gondii or bacterial endotoxin-stimulated IFN-gamma production by NK-enriched spleen cells from severe combined immunodeficient mice. Moreover, potent NK cytokine responses were induced by the combination of IL-12 and tumor necrosis factor alpha. In addition, adherent spleen cells from scid/scid mice or thyoglycollate-elicited macrophages from BALB/c animals produced high levels of both IL-12 (p40) and tumor necrosis factor alpha mRNAs when exposed to either live tachyzoites, parasite extracts, or endotoxin, confirming that these cytokines are produced by accessory cells. Finally, in vivo studies showed that treatment with recombinant IL-12 results in prolonged survival of scid mice after infection with T. gondii by means of a response dependent on both IFN-gamma and NK cells. Together the data argue that IL-12 is required for the T-cell-independent triggering of NK cells by intracellular parasites and that the cytokine may be useful for inducing this protective pathway in immunodeficient hosts.

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Metadata

Authors
Gazzinelli, R. T., Hieny, S., Wynn, T. A., Wolf, S., & Sher, A.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
1993-07
Volume
90
Issue
13
Pages
6115-6119
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.90.13.6115
OpenAlex
W2028500185
Cited by
835
References
22
FWCI
43.47
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Interleukin 12 is required for the T-lymphocyte-independent induction of interferon gamma by an intracellular parasite and induces resistance in T-cell-deficient hosts. https://app.cochat.ai/papers/10.1073/pnas.90.13.6115
The paper
Gazzinelli, R. T., Hieny, S., Wynn, T. A., Wolf, S., & Sher, A. (1993). Interleukin 12 is required for the T-lymphocyte-independent induction of interferon gamma by an intracellular parasite and induces resistance in T-cell-deficient hosts. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.90.13.6115

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.