Biology Reference
In-Depth Information
ch
1
Overview of the immune biology
of allogeneic hematopoietic
stem cell transplantation
Gérard Socié
Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, Université Paris VII Denis-Diderot, and Unité
INSERM U940, Paris, France
Bruce R Blazar
Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota,
Minneapolis, Minnesota, USA
1
Introduction
Much of our understanding of the biology of graft-versus-host disease
(GVHD) has developed from two preclinical animal models, the mouse
and the dog (reviewed in references
[1-6]
). Since there are significant spe-
cies differences between humans and mice, five points are important to
consider when drawing conclusions from studies with animal models and
before correlation to the clinical allogeneic hematopoietic stem cell trans-
plantation (HSCT) scenario (
Box 1.1
).
In this overview we introduce the main concepts and experimental results
concerning the major areas developed in the topic including the GVHD, the
graft-versus-leukemia (GVL) effect, rejection and immune deficiency.
We will focus on recent advances and their translation into clinical knowl-
edge or therapies. In each section we summarize key experimental data and
then provide a perspective as to how these data succeeded or failed to be
translated to the bedside. The main differences between experimental sys-
tems and human beings, as well the tools used to study GVHD and GVL, are
illustrated in
Figure 1.1
.
Immune rejection
Preclinical studies show that allogeneic hematopoietic stem cell (HSC) graft
rejection can be mediated by host natural killer (NK) cells, NK T cells, γδ T
cells, and/or CD4
+
and CD8
+
T cells that recognize histocompatibility anti-
gens (MiHA) on the donor cells (reviewed in chapter 5, and in references [6]
and [7]). In clinical practice, graft rejection of related HLA-identical bone
marrow (BM) or mobilized peripheral blood (PB) after myeloablative con-
ditioning is rare. Graft rejection or graft failure occurs primarily following
Search WWH ::
Custom Search