The cyclin dependent kinase inhibitor (R)-roscovitine mediates selective suppression of alloreactive human T cells but preserves pathogen-specific and leukemia-specific effectors

The cyclin dependent kinase inhibitor (R)-roscovitine mediates selective suppression of alloreactive human T cells but preserves pathogen-specific and leukemia-specific effectors

Copyright © 2014 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 152(2014), 1-2 vom: 01. Mai, Seite 48-57
1. Verfasser: Nellore, Anoma (VerfasserIn)
Weitere Verfasser: Liu, Bianling, Patsoukis, Nikolaos, Boussiotis, Vassiliki A, Li, Lequn
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2014
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Cdk2 Graft versus host disease T cells T regulatory cells Protein Kinase Inhibitors Purines WT1 Proteins mehr... WT1 protein, human Roscovitine 0ES1C2KQ94 Interferon-gamma 82115-62-6 EZH2 protein, human EC 2.1.1.43 Enhancer of Zeste Homolog 2 Protein Polycomb Repressive Complex 2 Cyclin-Dependent Kinase 2 EC 2.7.11.22
Beschreibung
Zusammenfassung:Copyright © 2014 Elsevier Inc. All rights reserved.
Graft versus host disease (GvHD), mediated by donor T cells, remains the primary cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation and novel therapeutic approaches are required. Cdk2 is a critical node of signal integration and programming of T cell responses towards immunity versus anergy but is dispensable for hematopoiesis and thymocyte development. We examined the effects of pharmacologic Cdk2 inhibition on alloreactive human T cells. Inhibition of Cdk2 blocked expansion of alloreactive T cells upon culture with HLA-mismatched dendritic cells and prevented generation of IFN-γ-producing alloantigen-specific effectors. In contrast, Cdk2 inhibition preserved effectors specific for Wilms' tumor 1 (WT1) leukemia antigen and for CMV as determined by WT1-specific and CMV-specific pentamers. Cdk2 inhibition preserved Treg cells, which have the ability to prevent GvHD while maintaining GvL. Thus, Cdk inhibitors may improve allogeneic HSCT by reducing alloreactivity and GvHD without loss of pathogen-specific and leukemia-specific immunity
Beschreibung:Date Completed 02.07.2014
Date Revised 13.12.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2014.02.015