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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1996-6-13
|
| pubmed:abstractText |
We have previously shown that T cell receptor-activated mouse T helper (Th)1 clones induce the production of interleukin (IL)-12 by splenic antigen-presenting cells (APC). Here, we show that the expression of CD40L by activated T cells is critical for T cell-dependent IL-12 production by mouse macrophages. IL-12 was produced in cultures containing alloreactive Th1 clones stimulated with allogeneic peritoneal macrophages, or in cultures of splenocytes stimulated with anti-CD3. Anti-CD40L monoclonal antibodies (mAb) inhibited the production of IL-12, but not IL-2, in these cultures by approximately 90% and had dramatic inhibitory effects on antigen-dependent proliferation of Th1 clones. In addition, both activated T cells and a Th1 clone derived from CD40L knockout mice failed to induce IL-12 production from splenic APC or peritoneal macrophages. Finally, macrophages cultured in the absence of T cells produced IL-12 upon stimulation with soluble recombinant CD40L in combination with either supernatants from activated Th1 clones or with interferon-gamma and granulocyte/macrophage colony-stimulating factor. Thus, both CD40L-dependent and cytokine-mediated signals from activated T cells are required to induce the production of IL-12 by macrophages. A blockade at the level of IL-12 production may explain, at least in part, the dramatic ability of anti-CD40L mAb to inhibit disease in animal models that are dependent upon the generation of a cell-mediated immune response. Moreover, a defect in T cell-dependent induction of IL-12 may contribute to the immune status of humans that lack functional CD40L.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/CD40 Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0014-2980
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
26
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
370-8
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8617306-Animals,
pubmed-meshheading:8617306-Antibodies, Monoclonal,
pubmed-meshheading:8617306-Antigens, CD40,
pubmed-meshheading:8617306-CD40 Ligand,
pubmed-meshheading:8617306-Cell-Free System,
pubmed-meshheading:8617306-Clone Cells,
pubmed-meshheading:8617306-Cytokines,
pubmed-meshheading:8617306-Drug Interactions,
pubmed-meshheading:8617306-Female,
pubmed-meshheading:8617306-Interleukin-12,
pubmed-meshheading:8617306-Lymphocyte Activation,
pubmed-meshheading:8617306-Macrophages, Peritoneal,
pubmed-meshheading:8617306-Male,
pubmed-meshheading:8617306-Membrane Glycoproteins,
pubmed-meshheading:8617306-Mice,
pubmed-meshheading:8617306-Mice, Inbred BALB C,
pubmed-meshheading:8617306-Mice, Inbred C57BL,
pubmed-meshheading:8617306-Mice, Inbred DBA,
pubmed-meshheading:8617306-Mice, Knockout,
pubmed-meshheading:8617306-Recombinant Proteins,
pubmed-meshheading:8617306-T-Lymphocytes,
pubmed-meshheading:8617306-T-Lymphocytes, Helper-Inducer
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
CD40/CD40 ligand interactions are required for T cell-dependent production of interleukin-12 by mouse macrophages.
|
| pubmed:affiliation |
Immunex Corporation, Seattle, USA.
|
| pubmed:publicationType |
Journal Article
|