Linked Life Data

7514125

Source:http://linkedlifedata.com/resource/pubmed/id/7514125

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1994-6-14
pubmed:abstractText
The CD28/CTLA-4 receptors on T cells interact with the B7 molecule on antigen-presenting cells (APC) to produce a co-stimulatory signal that determines the outcome of activation. The role of this co-stimulatory signal in T cell activation and loss of tolerance in autoimmune MRL-lpr/lpr mice has not been investigated previously. The present study examines the contribution of the CD28/CTLA-4 co-stimulatory pathway to the loss of T cell tolerance in V beta 8 transgenic MRL-lpr/lpr and (-)+/+ mice in which neonatal tolerance has been induced by the superantigen staphylococcal enterotoxin B (SEB). An artificial APC transfected with the murine B7 gene, and a CTLA-4-Ig fusion protein were used to analyze the significance of the CD28/CTLA-4 pathway in vitro. The CTLA-4-Ig fusion protein was also used to inhibit the pathway in vivo. Our results demonstrate that CD28 and CTLA-4 mRNA was overexpressed in the lymph nodes of lpr/lpr mice (MRL, C57BL/6, C3H and AKR), but not in +/+ mice of the same background strain. Lymph node T cells and thymocytes from SEB neonatally tolerized MRL-lpr/lpr mice that had undergone tolerance loss, proliferated when cultured with SEB and B7+ fibroblasts in vitro, but did not proliferate when the SEB was presented in the context of B7- fibroblasts. This in vitro tolerance loss could be prevented by blocking of B7 signaling by CTLA-4-Ig. This loss of tolerance did not occur in lymph node T cells from thymectomized MRL-lpr/lpr mice. SEB challenge of tolerized MRL-lpr/lpr mice in vivo led to weight loss, increased serum cytokine levels and depletion of V beta 8+ T cells. These effects were blocked by blocking of the co-stimulatory pathway by treatment with the CTLA-4-Ig fusion protein prior to and during challenge with SEB. T cells from thymus and lymph nodes of these mice did not proliferate later in response to stimulation in vitro with SEB even in the presence of B7+ APC. Nonresponsiveness was not due to deletion of V beta 8+ CD28+ T cells, as the number of these cells was increased after treatment with SEB and the CTLA-4-Ig fusion protein.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:geneSymbol
lpr
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1019-25
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:7514125-Animals, pubmed-meshheading:7514125-Antigens, CD, pubmed-meshheading:7514125-Antigens, CD28, pubmed-meshheading:7514125-Antigens, CD80, pubmed-meshheading:7514125-Antigens, Differentiation, pubmed-meshheading:7514125-Autoimmune Diseases, pubmed-meshheading:7514125-CTLA-4 Antigen, pubmed-meshheading:7514125-Cell Line, pubmed-meshheading:7514125-Clonal Anergy, pubmed-meshheading:7514125-Enterotoxins, pubmed-meshheading:7514125-Immunoconjugates, pubmed-meshheading:7514125-Lymphocyte Activation, pubmed-meshheading:7514125-Mice, pubmed-meshheading:7514125-Mice, Mutant Strains, pubmed-meshheading:7514125-Mice, Transgenic, pubmed-meshheading:7514125-Receptors, Antigen, T-Cell, pubmed-meshheading:7514125-T-Lymphocytes, pubmed-meshheading:7514125-Thymus Gland, pubmed-meshheading:7514125-Transfection, pubmed-meshheading:7514125-Weight Loss
pubmed:year
1994
pubmed:articleTitle
T cells of staphylococcal enterotoxin B-tolerized autoimmune MRL-lpr/lpr mice require co-stimulation through the B7-CD28/CTLA-4 pathway for activation and can be reanergized in vivo by stimulation of the T cell receptor in the absence of this co-stimulatory signal.
pubmed:affiliation
Department of Medicine, University of Alabama at Birmingham.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.