Theileria parva-transformed T cells show enhanced resistance to Fas/Fas ligand-induced apoptosis.

Détails

ID Serval
serval:BIB_8849F59380F2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Theileria parva-transformed T cells show enhanced resistance to Fas/Fas ligand-induced apoptosis.
Périodique
Journal of Immunology
Auteur(s)
Küenzi P., Schneider P., Dobbelaere D.A.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2003
Volume
171
Numéro
3
Pages
1224-1231
Langue
anglais
Résumé
Lymphocyte homeostasis is regulated by mechanisms that control lymphocyte proliferation and apoptosis. Activation-induced cell death is mediated by the expression of death ligands and receptors, which, when triggered, activate an apoptotic cascade. Bovine T cells transformed by the intracellular parasite Theileria parva proliferate in an uncontrolled manner and undergo clonal expansion. They constitutively express the death receptor Fas and its ligand, FasL but do not undergo apoptosis. Upon elimination of the parasite from the host cell by treatment with a theilericidal drug, cells become increasingly sensitive to Fas/FasL-induced apoptosis. In normal T cells, the sensitivity to death receptor killing is regulated by specific inhibitor proteins. We found that anti-apoptotic proteins such as cellular (c)-FLIP, which functions as a catalytically inactive form of caspase-8, and X-chromosome-linked inhibitor of apoptosis protein (IAP) as well as c-IAP, which can block downstream executioner caspases, are constitutively expressed in T. parva-transformed T cells. Expression of these proteins is rapidly down-regulated upon parasite elimination. Antiapoptotic proteins of the Bcl-2 family such as Bcl-2 and Bcl-x(L) are also expressed but, in contrast to c-FLIP, c-IAP, and X-chromosome-linked IAP, do not appear to be tightly regulated by the presence of the parasite. Finally, we show that, in contrast to the situation in tumor cells, the phosphoinositide 3-kinase/Akt pathway is not essential for c-FLIP expression. Our findings indicate that by inducing the expression of antiapoptotic proteins, T. parva allows the host cell to escape destruction by homeostatic mechanisms that would normally be activated to limit the continuous expansion of a T cell population.
Mots-clé
Animals, Antigens, CD95/biosynthesis, Antigens, CD95/physiology, Antiprotozoal Agents/pharmacology, Apoptosis/immunology, CASP8 and FADD-Like Apoptosis Regulating Protein, Carrier Proteins/biosynthesis, Caspases/metabolism, Cattle, Cell Line, Transformed, Enzyme Activation/immunology, Fas Ligand Protein, Homeostasis/immunology, Host-Parasite Interactions/immunology, Immunity, Innate, Inhibitor of Apoptosis Proteins, Intracellular Signaling Peptides and Proteins, Ligands, Membrane Glycoproteins/biosynthesis, Membrane Glycoproteins/physiology, Naphthoquinones/pharmacology, Protein Biosynthesis, Proteins, T-Lymphocyte Subsets/cytology, T-Lymphocyte Subsets/enzymology, Theileria parva/drug effects, Theileria parva/growth &amp, development, Up-Regulation/immunology, X-Linked Inhibitor of Apoptosis Protein
Pubmed
Web of science
Création de la notice
19/01/2008 17:31
Dernière modification de la notice
20/08/2019 14:47
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