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.
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DOI：
10.1016/j.clim.2014.02.015
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Nellore A;Liu B;Patsoukis N;Boussiotis VA;Li L
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.
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DOI：
10.1111/j.1432-1033.1997.t01-2-00527.x
发表时间：
1997-01-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Meijer, L;Borgne, A;Moulinoux, JP
通讯作者：
Moulinoux, JP
DOI：
10.1016/j.bbadis.2007.07.001
发表时间：
2007-10-01
影响因子：
6.2
作者：
He, Lizhi;Fan, Catherine;Tang, Damu
通讯作者：
Tang, Damu
影响因子：
7.3
作者：
Patsoukis N;Brown J;Petkova V;Liu F;Li L;Boussiotis VA
通讯作者：
Boussiotis VA
影响因子：
6.2
作者：
Pezzotta, Anna;Mister, Martlena;Noris, Marina
通讯作者：
Noris, Marina
影响因子：
7.5
作者：
Harbour, JW;Dean, DC
通讯作者：
Dean, DC