期刊
BLOOD
卷 112, 期 13, 页码 5254-5258出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-03-147322
关键词
-
类别
资金
- National Institutes of Health (NIH, Bethesda, MD) [HL69929, CA33049, CA023766, CA107096]
- Leukemia & Lymphoma Society (White Plains, NY)
- Ryan Gibson Foundation (Dallas, TX)
- Emerald Foundation (New York, NY)
- Byrne Fund (Etna, NH)
- Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center
- Commonwealth Foundation for Cancer Research (Richmond, VA)
- National Marrow Donor Program (NMDP, Minneapolis, MN)
- Marrow Foundation (Minneapolis, MN)
- NIH [P20-CA103694]
- Lymphoma Research Foundation (NewYork, NY)
Graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation, and donor T cells are indispensable for GVHD. Current therapies have limited efficacy, selectivity, and high toxicities. We used a novel flow cytometry technique for the analysis of intracellular phosphorylation events in single cells in murine BMT models to identify and validate novel GVHD drug targets.(1-7) This method circumvents the requirement for large numbers of purified cells, unlike western blots. We defined a signaling profile for alloactivated T cells in vivo and identified the phosphorylation of ERK1/2 and STAT-3 as important events during T-cell ( allo) activation in GVHD. We establish that interference with STAT-3 phosphorylation can inhibit T-cell activation and proliferation in vitro and GVHD in vivo. This suggests that phosphospecific flow cytometry is useful for the identification of promising drug targets, and ERK1/2 and STAT-3 phosphorylation in alloactivated T cells may be important for GVHD. (Blood. 2008; 112: 5254-5258)
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