Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
|
pubmed:dateCreated |
1994-12-22
|
pubmed:abstractText |
The 65-kDa isoform of glutamic acid decarboxylase (GAD65) has been implicated in autoimmune diabetes in NOD mice, but the role of the 67-kDa GAD isoform (GAD67) is less clear. We found that immunization of 4-week-old NOD mice with purified recombinant mouse GAD67 prevented or significantly delayed the onset of diabetes. To further explore this phenomenon, we characterized anti-GAD67 immune responses in naive and GAD-immunized NOD mice. Anti-GAD67 antibodies titers were relatively low in naive mice at all ages, but a single immunization with GAD67 at 4 weeks induced high titers of anti-GAD antibodies by 6 weeks of age. In both 4-week-old and diabetic NOD mice, there were significant endogenous T-cell proliferative responses against purified recombinant mouse GAD67. These T-cell proliferative responses were blocked by anti-I-ANOD and anti-CD4 antibodies. To characterize the anti-GAD T-cell responses in the NOD mice, we established T-cell lines and T-cell clones which recognized GAD67, and we used recombinant subfragments of GAD to localize the predominant T-cell epitopes in GAD67. T-cells from naive NOD mice proliferated in response to all GAD subfragments, whereas T-cells from diabetic mice responded primarily to the COOH-terminal 83 amino acids of GAD67. These results suggest that GAD67 is an autoantigen in IDDM and immunization of prediabetic NOD mice with GAD67 can prevent the onset of diabetes.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
AIM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Autoantigens,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate Decarboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-D Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
|
pubmed:status |
MEDLINE
|
pubmed:month |
Dec
|
pubmed:issn |
0012-1797
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
43
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1494-9
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:7525393-Animals,
pubmed-meshheading:7525393-Antibodies,
pubmed-meshheading:7525393-Antigens, CD4,
pubmed-meshheading:7525393-Autoantigens,
pubmed-meshheading:7525393-Autoimmune Diseases,
pubmed-meshheading:7525393-Base Sequence,
pubmed-meshheading:7525393-Diabetes Mellitus, Type 1,
pubmed-meshheading:7525393-Epitopes,
pubmed-meshheading:7525393-Glutamate Decarboxylase,
pubmed-meshheading:7525393-HLA-D Antigens,
pubmed-meshheading:7525393-Immunization,
pubmed-meshheading:7525393-Lymphocyte Activation,
pubmed-meshheading:7525393-Mice,
pubmed-meshheading:7525393-Mice, Inbred NOD,
pubmed-meshheading:7525393-Molecular Sequence Data,
pubmed-meshheading:7525393-Peptide Fragments,
pubmed-meshheading:7525393-Recombinant Proteins,
pubmed-meshheading:7525393-T-Lymphocytes
|
pubmed:year |
1994
|
pubmed:articleTitle |
Immunization with the larger isoform of mouse glutamic acid decarboxylase (GAD67) prevents autoimmune diabetes in NOD mice.
|
pubmed:affiliation |
Department of Immunology, University of Alberta, Edmonton, Canada.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|