|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0012854,
umls-concept:C0021641,
umls-concept:C0032136,
umls-concept:C0085243,
umls-concept:C0205734,
umls-concept:C0449258,
umls-concept:C0679058,
umls-concept:C1280500,
umls-concept:C1547699,
umls-concept:C1569894,
umls-concept:C2700640
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2001-6-21
|
|
pubmed:abstractText |
We previously demonstrated that administration of plasmid DNAs (pDNAs) encoding IL-4 and a fragment of glutamic acid decarboxylase 65 (GAD65) fused to IgGFc induces GAD65-specific Th2 cells and prevents insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. To assess the general applicability of pDNA vaccination to mediate Ag-specific immune deviation, we examined the immunotherapeutic efficacy of recombinants encoding murine insulin A and B chains fused to IgGFc. Insulin was chosen based on studies demonstrating that administration of insulin or insulin B chain by a variety of strategies prevents IDDM in NOD mice. Surprisingly, young NOD mice receiving i.m. injections of pDNA encoding insulin B chain-IgGFc with or without IL-4 exhibited an accelerated progression of insulitis and developed early diabetes. Exacerbation of IDDM correlated with an increased frequency of IFN-gamma-secreting CD4(+) and CD8(+) T cells in response to insulin B chain-specific peptides compared with untreated mice. In contrast, treatment with pDNAs encoding insulin A chain-IgGFc and IL-4 elicited a low frequency of IL-4-secreting Th cells and had no effect on the progression of IDDM. Vaccination with pDNAs encoding GAD65-IgGFc and IL-4, however, prevented IDDM. These results demonstrate that insulin- and GAD65-specific T cell reactivity induced by pDNA vaccination has distinct effects on the progression of IDDM.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate Decarboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fc Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA,
http://linkedlifedata.com/resource/pubmed/chemical/glutamate decarboxylase 2
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
0022-1767
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
167
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
586-92
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
pubmed-meshheading:11418698-Aging,
pubmed-meshheading:11418698-Animals,
pubmed-meshheading:11418698-CD4-Positive T-Lymphocytes,
pubmed-meshheading:11418698-CD8-Positive T-Lymphocytes,
pubmed-meshheading:11418698-Diabetes Mellitus, Type 1,
pubmed-meshheading:11418698-Disease Progression,
pubmed-meshheading:11418698-Epitopes, T-Lymphocyte,
pubmed-meshheading:11418698-Female,
pubmed-meshheading:11418698-Glutamate Decarboxylase,
pubmed-meshheading:11418698-Immunoglobulin Fc Fragments,
pubmed-meshheading:11418698-Immunoglobulin G,
pubmed-meshheading:11418698-Injections, Intramuscular,
pubmed-meshheading:11418698-Insulin,
pubmed-meshheading:11418698-Interleukin-4,
pubmed-meshheading:11418698-Isoenzymes,
pubmed-meshheading:11418698-Lymphocyte Activation,
pubmed-meshheading:11418698-Lymphocyte Count,
pubmed-meshheading:11418698-Mice,
pubmed-meshheading:11418698-Mice, Inbred NOD,
pubmed-meshheading:11418698-Plasmids,
pubmed-meshheading:11418698-Recombinant Fusion Proteins,
pubmed-meshheading:11418698-Th1 Cells,
pubmed-meshheading:11418698-Vaccines, DNA
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Plasmid DNAs encoding insulin and glutamic acid decarboxylase 65 have distinct effects on the progression of autoimmune diabetes in nonobese diabetic mice.
|
|
pubmed:affiliation |
Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
