Source:http://linkedlifedata.com/resource/pubmed/id/15728489
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2005-2-24
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| pubmed:abstractText |
In the periphery, IL-18 synergistically induces the expression of the Th1 cytokine IFN-gamma in the presence of IL-12 and the Th2 cytokines IL-5 and IL-13 in the presence of IL-2. Although the expression of these cytokines has been described in the thymus, their role in thymic development and function remains uncertain. We report here that freshly isolated thymocytes from C57BL/6 and BALB/c mice stimulated in vitro with IL-2-plus-IL-18 or IL-12-plus-IL-18 produce large amounts of IFN-gamma and IL-13. Analysis of the thymic subsets, CD4(-)CD8(-) (DN), CD4(+)CD8(+), CD4(+)CD8(-), and CD4(-)CD8(+) revealed that IL-18 in combination with IL-2 or IL-12 induces IFN-gamma and IL-13 preferentially from DN cells. Moreover, DN2 and DN3 thymocytes contained more IFN-gamma(+) cells than cells in the later stage of maturation. Additionally, IL-18 in combination with IL-2 induces CCR4 (Th2-associated) and CCR5 (Th1-associated) gene expression. In contrast, IL-18-plus-IL-12 specifically induced CCR5 expression. The IL-2-plus-IL-18 or IL-12-plus-IL-18 effect on IFN-gamma and IL-13 expression is dependent on Stat4 and NF-kappaB but independent of Stat6, T-bet, or NFAT. Furthermore, IL-12-plus-IL-18 induces significant thymocyte apoptosis when expressed in vivo or in vitro, and this effect is exacerbated in the absence of IFN-gamma. IL-12-plus-IL-18-stimulated thymocytes can also induce IA-IE expression on cortical and medullary thymic epithelial cells in an IFN-gamma-dependent manner. Thus, the combination of IL-2, IL-12, and IL-18 can induce phenotypic and functional changes in thymocytes that may alter migration, differentiation, and cell death of immature T cells inside the thymus and potentially affect the Th1/Th2 bias in peripheral immune compartments.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Ccr4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-13,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR4,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR5,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
|
| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
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| pubmed:volume |
174
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2796-804
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:15728489-Adjuvants, Immunologic,
pubmed-meshheading:15728489-Animals,
pubmed-meshheading:15728489-Apoptosis,
pubmed-meshheading:15728489-Cell Differentiation,
pubmed-meshheading:15728489-Cells, Cultured,
pubmed-meshheading:15728489-Cytokines,
pubmed-meshheading:15728489-Dose-Response Relationship, Immunologic,
pubmed-meshheading:15728489-Drug Combinations,
pubmed-meshheading:15728489-Interferon-gamma,
pubmed-meshheading:15728489-Interleukin-12,
pubmed-meshheading:15728489-Interleukin-13,
pubmed-meshheading:15728489-Interleukin-18,
pubmed-meshheading:15728489-Interleukin-2,
pubmed-meshheading:15728489-Mice,
pubmed-meshheading:15728489-Mice, Inbred BALB C,
pubmed-meshheading:15728489-Mice, Inbred C57BL,
pubmed-meshheading:15728489-Mice, Knockout,
pubmed-meshheading:15728489-Mice, Transgenic,
pubmed-meshheading:15728489-Receptors, CCR4,
pubmed-meshheading:15728489-Receptors, CCR5,
pubmed-meshheading:15728489-Receptors, Chemokine,
pubmed-meshheading:15728489-T-Lymphocyte Subsets,
pubmed-meshheading:15728489-Th1 Cells,
pubmed-meshheading:15728489-Th2 Cells,
pubmed-meshheading:15728489-Thymus Gland
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| pubmed:year |
2005
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| pubmed:articleTitle |
Synergistic effect of IL-2, IL-12, and IL-18 on thymocyte apoptosis and Th1/Th2 cytokine expression.
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| pubmed:affiliation |
Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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