In vivo imaging of graftversus-host disease and graftversus-leukemia - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 58

ch 4

In vivo imaging of graft-
versus-host disease and graft-
versus-leukemia

Dennis B Leveson-Gower, Robert S Negrin
Division of Blood and Marrow Transplantation, Stanford University, Stanford, California, USA

Introduction

59

In vivo imaging provides unique insights into complex biological pro-
cesses. It has many advantages and often replaces more cumbersome
and inaccurate methods, such as measuring tumor volume with calipers,
with more elegant technologies which more accurately determine volume
and location. Also, in vivo imaging has allowed for the temporal study of
individual animals over time, greatly reducing the number of animals and
enhancing statistical power needed to conduct a study. These advances are
in alignment with the policies of most animal welfare regulation boards
which generally adhere to the three “Rs”: replacement, reduction and
refinement.

Although a great deal has and will be learned from in vitro assays and ex vivo
analysis of tissues following transplantation, the development of in vivo
imaging technologies has taught us a great deal about the pathogenesis
of graft-versus-host disease (GVHD) as well as the graft-versus-leukemia
(GVL) effect in hematopoietic cell transplantation (HCT). The spatial and
temporal kinetics of disease initiation and progression have been revealed
which allows for study of the trafficking behavior of various immune cells.
This has facilitated a deeper understanding of where important interactions
between donor and host cells occur, and has highlighted where therapeu-
tic interventions might have the most impact. With the study of regulating
GVHD, in vivo imaging of T-cell proliferation has effectively replaced artifi-
cial in vitro mixed-leukocyte assays with real-time monitoring of T-cell pro-
liferation in vivo . Additionally in vivo imaging has elucidated that different
immunoregulatory cells and drugs have a diverse impact on T-cell biology
including inhibition of proliferation, vesicle adhesion and rolling, lymph
node egress and tissue homing.

This chapter will provide an overview of some of the most dynamic and
insightful in vivo imaging technologies ( Table 4.1 ) which have been applied
to the study of GVHD and GVL in small animal models. We also want to
highlight some of the most interesting and important observations that
have been made through the application of these imaging modalities.