کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6087546 1589429 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The cyclin dependent kinase inhibitor (R)-roscovitine mediates selective suppression of alloreactive human T cells but preserves pathogen-specific and leukemia-specific effectors
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
The cyclin dependent kinase inhibitor (R)-roscovitine mediates selective suppression of alloreactive human T cells but preserves pathogen-specific and leukemia-specific effectors
چکیده انگلیسی


- Inhibition of Cdk2 blocked expansion of alloreactive human T cells.
- Inhibition of Cdk2 preserved WT1- and CMV-specific effectors.
- Inhibition of Cdk2 preserved and increased Treg cells.
- Inhibition of Cdk2 suppressed expression and phosphorylation of EZH2.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Immunology - Volume 152, Issues 1–2, May–June 2014, Pages 48-57
نویسندگان
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