Linked Life Data

11490031

Source:http://linkedlifedata.com/resource/pubmed/id/11490031

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-8-7
pubmed:abstractText
Transgenic restoration of normally absent H2-E MHC class II molecules on APC dominantly inhibits T cell-mediated autoimmune diabetes (IDDM) in nonobese diabetic (NOD) mice. We analyzed the minimal requirements for transgenic H2-E expression on APC subtypes (B lymphocytes vs macrophages/dendritic cells (DC)) to inhibit IDDM. This issue was addressed through the use of NOD stocks transgenically expressing high levels of H2-E and/or made genetically deficient in B lymphocytes in a series of genetic intercross and bone marrow/lymphocyte chimera experiments. Standard (H2-E(null)) NOD B lymphocytes exert a pathogenic function(s) necessary for IDDM. However, IDDM was inhibited in mixed chimeras where H2-E was solely expressed on all B lymphocytes. Interestingly, this resistance was abrogated when even a minority of standard NOD H2-E(null) B lymphocytes were also present. In contrast, in NOD chimeras where H2-E expression was solely limited to approximately half the macrophages/DC, an active immunoregulatory process was induced that inhibited IDDM. Introduction of a disrupted IL-4 gene into the NOD-H2-E transgenic stock demonstrated that induction of this Th2 cytokine does not represent the IDDM protective immunoregulatory process mediated by H2-E expression. In conclusion, high numbers of multiple subtypes of APC must express H2-E MHC class II molecules to additively inhibit IDDM in NOD mice. This raises a high threshold for success in future intervention protocols designed to inhibit IDDM by introduction of putatively protective MHC molecules into hemopoietic precursors of APC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2404-10
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11490031-Animals, pubmed-meshheading:11490031-Antigen-Presenting Cells, pubmed-meshheading:11490031-B-Lymphocyte Subsets, pubmed-meshheading:11490031-Diabetes Mellitus, Type 1, pubmed-meshheading:11490031-Female, pubmed-meshheading:11490031-Gene Expression Regulation, pubmed-meshheading:11490031-H-2 Antigens, pubmed-meshheading:11490031-HLA-DR Antigens, pubmed-meshheading:11490031-Immunity, Innate, pubmed-meshheading:11490031-Interleukin-4, pubmed-meshheading:11490031-Macrophages, pubmed-meshheading:11490031-Male, pubmed-meshheading:11490031-Mice, pubmed-meshheading:11490031-Mice, Inbred NOD, pubmed-meshheading:11490031-Mice, Transgenic, pubmed-meshheading:11490031-Sequence Homology, Amino Acid, pubmed-meshheading:11490031-Th2 Cells, pubmed-meshheading:11490031-Transgenes
pubmed:year
2001
pubmed:articleTitle
Inhibition of autoimmune diabetes in nonobese diabetic mice by transgenic restoration of H2-E MHC class II expression: additive, but unequal, involvement of multiple APC subtypes.
pubmed:affiliation
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't