Linked Life Data

11859117

Source:http://linkedlifedata.com/resource/pubmed/id/11859117

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-2-22
pubmed:abstractText
Negative selection is a process to delete potentially autoreactive clones in developing thymocytes. Programmed cell death or apoptosis is thought to play an important role in this selection process. In this study, we investigated the role of apoptotic protease-activating factor 1 (Apaf1), a mammalian homologue of CED-4, in programmed cell death during the negative selection in thymus. There was no developmental abnormality in thymocytes from newborn Apaf1(-/-) mice in terms of CD4 and CD8 expression pattern and thymocyte number. Clonal deletion by endogenous male H-Y Ag of Apaf1-deficient thymocytes with transgenic expression of H-Y Ag-specific TCRs (H-Y Tg/Apaf1(-/-) thymocytes) was normally observed in lethally irradiated wild-type mice reconstituted with fetal liver-derived hemopoietic stem cells. Clonal deletion induced in vitro by a bacterial superantigen was also normal in fetal thymic organ culture. Thus, Apaf1-mediated pathway of apoptosis is dispensable for the negative selection of thymocytes. However, H-Y Tg/Apaf1(-/-) thymocytes showed partial resistance to H-Y peptide-induced deletion in vitro as compared with H-Y Tg/Apaf1(+/-) thymocytes, implicating the Apaf1-mediated apoptotic pathway in the negative selection in a certain situation. In addition, the peptide-induced deletion was still observed in H-Y Tg/Apaf1(-/-) thymocytes in the presence of a broad spectrum caspase inhibitor, z-VAD-fmk, suggesting the presence of caspase-independent cell death pathway playing roles during the negative selection. We assume that mechanisms for the negative selection are composed of several cell death pathways to avoid failure of elimination of autoreactive clones.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2288-95
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11859117-Animals, pubmed-meshheading:11859117-Apoptosis, pubmed-meshheading:11859117-Apoptotic Protease-Activating Factor 1, pubmed-meshheading:11859117-Cells, Cultured, pubmed-meshheading:11859117-Chimera, pubmed-meshheading:11859117-Clonal Deletion, pubmed-meshheading:11859117-Enterotoxins, pubmed-meshheading:11859117-Female, pubmed-meshheading:11859117-Genes, T-Cell Receptor, pubmed-meshheading:11859117-H-Y Antigen, pubmed-meshheading:11859117-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:11859117-Liver, pubmed-meshheading:11859117-Mice, pubmed-meshheading:11859117-Mice, Inbred C57BL, pubmed-meshheading:11859117-Mice, Knockout, pubmed-meshheading:11859117-Mice, Transgenic, pubmed-meshheading:11859117-Organ Culture Techniques, pubmed-meshheading:11859117-Proteins, pubmed-meshheading:11859117-Self Tolerance, pubmed-meshheading:11859117-Signal Transduction, pubmed-meshheading:11859117-Superantigens, pubmed-meshheading:11859117-T-Lymphocytes, pubmed-meshheading:11859117-Thymus Gland
pubmed:year
2002
pubmed:articleTitle
The apoptotic protease-activating factor 1-mediated pathway of apoptosis is dispensable for negative selection of thymocytes.
pubmed:affiliation
Department of Immunology and Technical Support Laboratory, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't