期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 19, 期 9, 页码 1331-1339出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2013.06.016
关键词
Dendritic cell T cell; IL-12; Graft-versus-leukemia
资金
- NCI NIH HHS [R01 CA188523, R01 CA074364] Funding Source: Medline
- NIAID NIH HHS [R56 AI145231] Funding Source: Medline
A critical question in the field of allogeneic hematopoietic stem cell transplantation (HSCT) is how to enhance graft-versus-leukemia (GVL) activity while limiting graft-versus-host-disease (GVHD). We have previously reported that donor bone marrow (BM) precursors of plasmacytoid dendritic cells (pre-pDCs) can polarize donor T cells toward Th1 immunity and augment the GVL activity of donor T cells while attenuating their GVHD activity in a murine model of allogeneic HSCT. Clinical data on the role of donor pre-pDCs and conventional DCs (cDCs) on transplantation outcomes has been conflicting. To test the effect of increasing the proportion of pre-pDCs versus cDCs in a BM graft, we enriched CD11b(-) pDCs by selectively depleting the CD11b(+) myeloid DC (mDC) population from BM using FACS sorting in a murine model of allogeneic BM transplantation. Donor T cell expansion and GVL activity were greater in mice that received BM depleted of mDCs compared with mice that received undepleted BM. GVHD was not increased by depleting mDCs. To examine the mechanism through which mDC depletion enhances the GVL activity of donor T cells, we used BM and pDCs from IL-12p40KO mice, and found that the increased GVL activity of mDC-depleted BM was IL-12-dependent. This study indicates that a clinically translatable strategy of engineering the DC content of grafts can improve clinical outcomes in allogeneic HSCT through the regulation of donor T cell activation and GVL activity. (C) 2013 American Society for Blood and Marrow Transplantation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据