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Blood. 2008 Dec 15;112(13):5254-8. doi: 10.1182/blood-2008-03-147322. Epub 2008 Oct 6.

STAT-3 and ERK 1/2 phosphorylation are critical for T-cell alloactivation and graft-versus-host disease.

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1
Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Abstract

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 phospho-specific 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.

PMID:
18838616
PMCID:
PMC2597618
DOI:
10.1182/blood-2008-03-147322
[Indexed for MEDLINE]
Free PMC Article
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