Linked Life Data

8496610

Source:http://linkedlifedata.com/resource/pubmed/id/8496610

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1993-6-22
pubmed:abstractText
To study self reactivity, a transgenic mouse model has been established in which the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) is expressed in the beta-islet cells of the pancreas (rat insulin promoter (RIP)-gp). These mice (H-2b) do not spontaneously develop diabetes; however, infection with the LCMV strain WE rapidly induces hyperglycemia. In this study, comparative analysis of H-2k RIP-gp-transgenic animals demonstrated that the haplotype influences the incidence and kinetics of diabetes and alters the requirement for the CD4+ T cell subset. This study also showed that the properties of the virus expressing the self target Ag determined whether hyperglycemia occurred in RIP-gp-transgenic mice. Various LCMV strains were able to induce diabetes in RIP-gp-transgenic animals, whereas infection with a recombinant vaccinia virus expressing LCMV-gp (vacc-gp) did not induce diabetes. However, vacc-gp could induce diabetes in double (RIP-gp/TCR)-transgenic mice, where the majority of CD8+ T cells expressed a receptor specific for LCMV-gp, suggesting that a critical number of self-reactive T cells must be activated to induce disease. Notably, histologic analysis of pancreata taken various days after LCMV or vacc-gp infections indicated that induction of diabetes coincided with an increase in MHC class I expression on the islets of Langerhans. Additional studies with vacc-gp were done to determine other factors that possibly enhance autoimmune attack. Transgenic mice expressing both LCMV-gp and TNF-alpha under the control of the RIP were infected with vacc-gp, and 50% of RIP-gp/TNF-alpha-transgenic animals became hyperglycemic. These data suggest that the increased local lymphocyte traffic as a result of TNF-alpha expression attracts activated gp-specific T cells, enhancing the possibility of hyperglycemia. Collectively, these results demonstrate that the induction of diabetes in this model is influenced by the MHC haplotype, the infectious agent, TNF-alpha expression, the level of MHC class I expression, and the induction of a threshold number of self-reactive CTL.
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
1
pubmed:volume
150
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5185-94
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8496610-Animals, pubmed-meshheading:8496610-Antigens, Viral, pubmed-meshheading:8496610-Base Sequence, pubmed-meshheading:8496610-Diabetes Mellitus, Experimental, pubmed-meshheading:8496610-Disease Susceptibility, pubmed-meshheading:8496610-Glycoproteins, pubmed-meshheading:8496610-Haplotypes, pubmed-meshheading:8496610-Histocompatibility Antigens Class I, pubmed-meshheading:8496610-Lymphocytic Choriomeningitis, pubmed-meshheading:8496610-Mice, pubmed-meshheading:8496610-Mice, Inbred C57BL, pubmed-meshheading:8496610-Mice, Transgenic, pubmed-meshheading:8496610-Molecular Sequence Data, pubmed-meshheading:8496610-Rats, pubmed-meshheading:8496610-T-Lymphocytes, Helper-Inducer, pubmed-meshheading:8496610-Tumor Necrosis Factor-alpha, pubmed-meshheading:8496610-Vaccinia virus
pubmed:year
1993
pubmed:articleTitle
Induction of diabetes is influenced by the infectious virus and local expression of MHC class I and tumor necrosis factor-alpha.
pubmed:affiliation
Department of Pathology, University of Zurich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't