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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1997-8-19
|
| pubmed:abstractText |
A new type of CD4+ T cell clone (NY4.2) isolated from pancreatic islet-infiltrated lymphocytes of acutely diabetic non-obese diabetic (NOD) mice prevents the development of insulin-dependent diabetes mellitus (IDDM) in NOD mice, as well as the recurrence of autoimmune diabetes in syngeneic islet-transplanted NOD mice. It has been demonstrated that the cytokine TGF-beta, secreted from the cells of this clone, is the substance which prevents autoimmune IDDM. This investigation was initiated to determine the molecular role TGF-beta plays in the prevention of autoimmune IDDM by determining its effect on IL-2-induced signal transduction in Con A-activated NOD mouse splenocytes and HT-2 cells. First, we determined whether TGF-beta, secreted from NY4.2 T cells, inhibits IL-2-dependent T cell proliferation in HT-2 cells (IL-2-dependent T cell line) and NOD splenocytes. We found that TGF-beta suppresses IL-2-dependent T cell proliferation. Second, we determined whether TGF-beta inhibits the activation of Janus kinases (JAKs), as well as signal transducers and activators of transcription (STAT) proteins, involved in an IL-2-induced signalling pathway that normally leads to the proliferation of T cells. We found that TGF-beta inhibited tyrosine phosphorylation of JAK1, JAK3, STAT3 and STAT5 in Con A blasts from NOD splenocytes and HT-2 cells. Third, we examined whether TGF-beta inhibits the cooperation between STAT proteins and mitogen-activated protein kinase (MAPK), especially extracellular signal-regulated kinase 2 (ERK2). We found that TGF-beta inhibited the association of STAT3 and STAT5 with ERK2 in Con A blasts from NOD splenocytes and HT-2 cells. On the basis of these observations, we conclude that TGF-beta may interfere with signal transduction via inhibition of the IL-2-induced JAK/STAT pathway and inhibition of the association of STAT proteins with ERK2 in T cells from NOD splenocytes, resulting in the inhibition of IL-2-dependent T cell proliferation. TGF-beta-mediated suppression of T cell activation may be responsible for the prevention of effector T cell-mediated autoimmune IDDM in NOD mice by TGF-beta-producing CD4+ suppressor T cells.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acute-Phase Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Jak1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Jak3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0896-8411
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
10
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
299-307
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9218758-Acute-Phase Proteins,
pubmed-meshheading:9218758-Animals,
pubmed-meshheading:9218758-CD4-Positive T-Lymphocytes,
pubmed-meshheading:9218758-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9218758-Cell Line,
pubmed-meshheading:9218758-DNA-Binding Proteins,
pubmed-meshheading:9218758-Diabetes Mellitus, Type 1,
pubmed-meshheading:9218758-Down-Regulation,
pubmed-meshheading:9218758-Enzyme Activation,
pubmed-meshheading:9218758-Interleukin-2,
pubmed-meshheading:9218758-Janus Kinase 1,
pubmed-meshheading:9218758-Janus Kinase 3,
pubmed-meshheading:9218758-Lymphocyte Activation,
pubmed-meshheading:9218758-Mice,
pubmed-meshheading:9218758-Mice, Inbred NOD,
pubmed-meshheading:9218758-Milk Proteins,
pubmed-meshheading:9218758-Phosphorylation,
pubmed-meshheading:9218758-Protein-Tyrosine Kinases,
pubmed-meshheading:9218758-Receptors, Interleukin-2,
pubmed-meshheading:9218758-STAT3 Transcription Factor,
pubmed-meshheading:9218758-STAT5 Transcription Factor,
pubmed-meshheading:9218758-T-Lymphocytes, Regulatory,
pubmed-meshheading:9218758-Trans-Activators,
pubmed-meshheading:9218758-Transforming Growth Factor beta
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Molecular role of TGF-beta, secreted from a new type of CD4+ suppressor T cell, NY4.2, in the prevention of autoimmune IDDM in NOD mice.
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| pubmed:affiliation |
Department of Microbiology and Infectious Diseases, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, The University of Calgary, Alberta, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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