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Activated T Cells Travel to Target Organs in Acute GvHD

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Blood First Edition Paper, prepublished online February 8, 2005

Submitted December 13, 2004

Accepted January 28, 2005

Leukocyte migration and graft-versus-host disease

Christian A Wysocki, Panoskaltsis-Mortari, Bruce R Blazar, and

S Serody*

Departments of Medicine, Microbiology and Immunology, and the

Lineberger Comprehensive Cancer Center, University of North Carolina

at Chapel Hill, Chapel Hill, NC, USA

Department of Pediatrics, Division of Pediatric Bone Marrow

Transplantation, and the University of Minnesota Cancer Center,

University of Minnesota, Minneapolis, MN, USA

Graft-versus-host disease (GVHD) remains a significant complication

of allogeneic bone marrow transplantation (allo-BMT). Acute GVHD is

mediated by immunocompetent donor T cells, which migrate to lymphoid

tissues soon after infusion, recognize host alloantigens, and become

activated upon interaction with host antigen presenting cells (APCs).

Recent work from our group and others suggests that activated

effector T cells exit lymphoid tissues and traffic to mucosal sites

and parenchymal target organs such as the GI tract, liver, lung, and

skin where they cause tissue damage. The molecular interactions

necessary for effector cell migration during GVHD have become the

focus of a growing body of research, as these interactions represent

potential therapeutic targets.

In this review we will discuss chemokine/chemokine receptor

interactions and adhesion molecules that have been shown to play

roles in effector cell migration in experimental GVHD models, and

discuss a potential model for the role of chemokines during the

activation phase of GVHD.

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