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17
Chemokines and
graft-versus-host disease
Kenneth R Cooke
Blood and Marrow Stem Cell Transplantation Program, Division of Hematology and Oncology, Department of Pediatrics
and Medicine, University Hospitals, Case Medical Center, Case Comprehensive Cancer Center, Cleveland, Ohio, USA
James M Coghill
Lineberger Comprehensive Cancer Center, Departments of Medicine, Microbiology, and Immunology, University of North
Carolina School of Medicine, Chapel Hill, North Carolina, USA
Gerhard C Hildebrandt
Hematologic Malignancies & BMT Program, Department of Medicine, Louisiana State University Health Sciences Center,
Shreveport, Louisiana, USA
Jonathan S Serody
Lineberger Comprehensive Cancer Center, Departments of Medicine, Microbiology, and Immunology, University of North
Carolina School of Medicine, Chapel Hill, North Carolina, USA
393
Introduction
Graft-versus-host disease (GVHD) remains the major barrier to successful
outcomes following allogeneic hematopoietic cell transplantation (HCT).
The pathophysiology of GVHD is complex and involves a variety of cell types
in both its generation and its subsequent pathologic manifestations
[1]
. The
development of GVHD is fundamentally dependent upon varying degrees
of major histocompatibility complex (MHC) antigenic disparity between
donor and recipient. As the GVH response intensifies, it ultimately involves
a vast array of cellular effectors that are linked by the actions of immuno-
regulatory proteins. Donor T-cell activation by host antigen-presenting cells
(APCs) lies at the center of this immunological storm. A growing body of
experimental and clinical data suggests that chemokines, a subset of cyto-
kines traditionally defined by their ability to mediate immune cell chemo-
taxis, play a role in this process. Our knowledge of chemokine biology has
expanded from considering these molecules solely as promoters of chemo-
taxis to considering them as factors that can affect leukocyte activation and
differentiation during an emerging immune response. The ability to deter-
mine the precise role(s) of chemokines in GVH responses is limited by the
pleiotropic effects these molecules have and by the differences that exist in
the animal models used to study GVHD. This chapter reviews and attempts
to reconcile occasional contradictory studies, at times drawing on investi-
gations that have examined the role of chemokines in models of solid organ
transplantation and autoimmune disease. In addition, since HCT is the only
curative treatment for a number of malignant diseases, assessing the role of
chemokines in cancer progression as well as GVHD may provide insight as
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