Defective TCR signaling events in glycosylphosphatidylinositol-deficient T cells derived from paroxysmal nocturnal hemoglobinuria patients.

Details

Serval ID
serval:BIB_10477
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Defective TCR signaling events in glycosylphosphatidylinositol-deficient T cells derived from paroxysmal nocturnal hemoglobinuria patients.
Journal
International Immunology
Author(s)
Romagnoli P., Bron C.
ISSN
0953-8178
Publication state
Published
Issued date
1999
Volume
11
Number
9
Pages
1411-1422
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
licence nationale
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic disorder characterized by the presence of abnormal cells of various hematopoietic cell lineages deficient in surface expression of glycosylphosphatidylinositol (GPI)-anchored molecules. By analyzing T cells isolated from patients affected with PNH, it was found that ex vivo GPI-deficient CD4(+) and CD8(+) peripheral T cells display a more naive phenotype as compared to wild-type cells. In addition, in vitro proliferative responses to allogeneic antigen-presenting cells were shown to be reduced in mutant T cells. To investigate the molecular basis responsible for defective T cell activation in GPI-deficient T cells, T cell lines and T cell clones were generated from patients affected with PNH. When stimulated with anti-CD3epsilon mAb, mutant cells displayed a significantly decreased activation of protein tyrosine kinase p56(lck). The decreased kinase activity was accompanied by a delayed TCR capping and internalization. Interestingly, protein tyrosine phosphorylation is not only quantitatively but also qualitatively affected, with one substrate being more intensively phosphorylated in mutant than in wild-type cells. These observations suggest that a defective activation of p56(lck) contributes to the depressed immune responses observed in GPI-deficient T cells derived from PNH patients.
Keywords
CD4-Positive T-Lymphocytes/drug effects, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/drug effects, CD8-Positive T-Lymphocytes/immunology, Calcium/metabolism, Dose-Response Relationship, Immunologic, Enzyme Activation, Glycosylphosphatidylinositols/physiology, Hemoglobinuria, Paroxysmal/immunology, Humans, Lymphocyte Activation/drug effects, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism, Phosphorylation, Protein-Tyrosine Kinases/metabolism, Receptors, Antigen, T-Cell/physiology, Receptors, Antigen, T-Cell, gamma-delta/metabolism, Signal Transduction
Pubmed
Web of science
Create date
19/11/2007 12:00
Last modification date
20/08/2019 12:37
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