ABSTRACT
Graft-vs.-host disease (GVHD) is a complex process that affects multiple tissues and
involves a variety of cell types in both its generation and subsequent pathological
manifestations. At the core of GVHD is an immune response involving donor T cells and
the genetically disparate recipient. From this seemingly simple immune interaction, the
GVH response intensifies and ultimately involves a vast array of cellular effectors that are
linked by the actions of immunoregulatory cytokines. Chemokines, a subset of cytokines
traditionally defined by their ability to mediate immune cell chemotaxis, may contribute to
this process. Our understanding of chemokine biology has expanded from considering
these molecules solely as promoters of chemotaxis to factors that can affect leukocyte
activation and differentiation during an emerging immune response. Our ability to
delineate the precise role(s) of chemokines in a GVH response is hampered by the
pleotropic effects these molecules have and by the differences that exist in the animal
models used to study GVHD. This review will attempt to survey and reconcile the
sometimes contradictory literature in this area of research, at times drawing on studies that
have examined the role of chemokines in other models of transplantation and disease.
Importantly, since hematopoietic stem cell transplantation (SCT) is often used as a
treatment for cancer, assessing the role of chemokines in tumor progression as well as
GVHD may provide insight as to how the function of chemokines may be exploited to
provide maximal therapeutic benefit after SCT.
