Source:http://linkedlifedata.com/resource/pubmed/id/16751419
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0003069,
umls-concept:C0027059,
umls-concept:C0032214,
umls-concept:C0035820,
umls-concept:C0039194,
umls-concept:C0085243,
umls-concept:C0085358,
umls-concept:C0205164,
umls-concept:C0205359,
umls-concept:C0443146,
umls-concept:C0669383,
umls-concept:C1332714,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1706438,
umls-concept:C1998548,
umls-concept:C2698600
|
| pubmed:issue |
12
|
| pubmed:dateCreated |
2006-6-5
|
| pubmed:abstractText |
In humans, spontaneous autoimmune attack against cardiomyocytes often leads to idiopathic dilated cardiomyopathy (IDCM) and life-threatening heart failure. HLA-DQ8 transgenic IAb knockout NOD mice (NOD.DQ8/Ab(0); DQA1*0301, DQB1*0302) develop spontaneous anticardiomyocyte autoimmunity with pathology very similar to human IDCM, but why the heart is targeted is unknown. In the present study, we first investigated whether NOD/Ab(0) mice transgenic for a different DQ allele, DQ6, (DQA1*0102, DQB1*0602) would also develop myocarditis. NOD.DQ6/Ab(0) animals showed no cardiac pathology, implying that DQ8 is specifically required for the myocarditis phenotype. To further characterize the cellular immune mechanisms, we established crosses of our NOD.DQ8/Ab(0) animals with Rag1 knockout (Rag1(0)), Ig H chain knockout (IgH(0)), and beta(2)-microglobulin knockout (beta(2)m(0)) lines. Adoptive transfer of purified CD4 T cells from NOD.DQ8/Ab(0) mice with complete heart block (an indication of advanced myocarditis) into younger NOD.DQ8/Ab(0) Rag1(0) animals induced cardiac pathology in all recipients, whereas adoptive transfer of purified CD8 T cells or B lymphocytes had no effect. Despite the absence of B lymphocytes, NOD.DQ8/Ab(0)IgH(0) animals still developed complete heart block, whereas NOD.DQ8/Ab(0)beta(2)m(0) mice (which lack CD8 T cells) failed to develop any cardiac pathology. CD8 T cells (and possibly NK cells) seem to be necessary to initiate disease, whereas once initiated, CD4 T cells alone can orchestrate the cardiac pathology, likely through their capacity to recruit and activate macrophages. Understanding the cellular immune mechanisms causing spontaneous myocarditis/IDCM in this relevant animal model will facilitate the development and testing of new therapies for this devastating disease.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
176
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
7715-25
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:16751419-Adoptive Transfer,
pubmed-meshheading:16751419-Animals,
pubmed-meshheading:16751419-Autoimmune Diseases,
pubmed-meshheading:16751419-CD4-Positive T-Lymphocytes,
pubmed-meshheading:16751419-CD8-Positive T-Lymphocytes,
pubmed-meshheading:16751419-Cardiomyopathy, Dilated,
pubmed-meshheading:16751419-Disease Models, Animal,
pubmed-meshheading:16751419-HLA-DQ Antigens,
pubmed-meshheading:16751419-Heart Block,
pubmed-meshheading:16751419-Histocompatibility Antigens Class II,
pubmed-meshheading:16751419-Humans,
pubmed-meshheading:16751419-Killer Cells, Natural,
pubmed-meshheading:16751419-Lymphocyte Transfusion,
pubmed-meshheading:16751419-Macrophages,
pubmed-meshheading:16751419-Mice,
pubmed-meshheading:16751419-Mice, Inbred NOD,
pubmed-meshheading:16751419-Mice, Knockout,
pubmed-meshheading:16751419-Mice, Transgenic
|
| pubmed:year |
2006
|
| pubmed:articleTitle |
CD4 T cells play major effector role and CD8 T cells initiating role in spontaneous autoimmune myocarditis of HLA-DQ8 transgenic IAb knockout nonobese diabetic mice.
|
| pubmed:affiliation |
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|