Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1999-6-16
pubmed:abstractText
Polyclonal, generalized T cell defects, as well as Ag-specific Th clones, are likely to contribute to pathology in murine lupus, but the genetic bases for these mechanisms remain unknown. Mapping studies indicate that loci on chromosomes 1 (Sle1), 4 (Sle2), 7 (Sle3), and 17 (Sle4) confer disease susceptibility in the NZM2410 lupus strain. B6.NZMc7 mice are C57BL/6 (B6) mice congenic for the NZM2410-derived chromosome 7 susceptibility interval, bearing Sle3. Compared with B6 controls, B6.NZMc7 mice exhibit elevated CD4:CD8 ratios (2.0 vs 1.34 in 1- to 3-mo-old spleens); an age-dependent accumulation of activated CD4+ T cells (33.4% vs 21.9% in 9- to 12-mo-old spleens); a more diffuse splenic architecture; and a stronger immune response to T-dependent, but not T-independent, Ags. In vitro, Sle3-bearing T cells show stronger proliferation, increased expansion of CD4+ T cells, and reduced apoptosis (with or without anti-Fas) following stimulation with anti-CD3. With age, the B cells in this strain acquire an activated phenotype. Thus, the NZM2410 allele of Sle3 appears to impact generalized T cell activation, and this may be causally related to the low grade, polyclonal serum autoantibodies seen in this strain. Epistatic interactions with other loci may be required to transform this relatively benign phenotype into overt autoimmunity, as seen in the NZM2410 strain.
pubmed:grant
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
162
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6492-502
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10352264-Animals, pubmed-meshheading:10352264-Antigens, T-Independent, pubmed-meshheading:10352264-Apoptosis, pubmed-meshheading:10352264-Chromosome Mapping, pubmed-meshheading:10352264-Dinitrobenzenes, pubmed-meshheading:10352264-Female, pubmed-meshheading:10352264-Genetic Markers, pubmed-meshheading:10352264-Genetic Predisposition to Disease, pubmed-meshheading:10352264-Haptens, pubmed-meshheading:10352264-Hemocyanin, pubmed-meshheading:10352264-Lipopolysaccharides, pubmed-meshheading:10352264-Lupus Erythematosus, Systemic, pubmed-meshheading:10352264-Lymphocyte Activation, pubmed-meshheading:10352264-Lymphocyte Subsets, pubmed-meshheading:10352264-Lymphoid Tissue, pubmed-meshheading:10352264-Male, pubmed-meshheading:10352264-Mice, pubmed-meshheading:10352264-Mice, Congenic, pubmed-meshheading:10352264-Mice, Inbred C57BL, pubmed-meshheading:10352264-Mice, Inbred NZB, pubmed-meshheading:10352264-T-Lymphocytes
pubmed:year
1999
pubmed:articleTitle
Genetic dissection of Sle pathogenesis: Sle3 on murine chromosome 7 impacts T cell activation, differentiation, and cell death.
pubmed:affiliation
Simmons Arthritis Research Center, Center for Immunology, University of Texas Southwestern Medical Center, Dallas 75235, USA. chandra.mohan@email.swmed.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't