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In vivo imaging using bioluminescence: a tool for probing graft-versus-host disease

Nature Reviews Immunology volume 6, pages 484–490 (2006)Cite this article

Abstract

Immunological reactions have a key role in health and disease and are complex events characterized by coordinated cell trafficking to specific locations throughout the body. Clarification of these cell-trafficking events is crucial for improving our understanding of how immune reactions are initiated, controlled and recalled. As we discuss here, an emerging modality for revealing cell trafficking is bioluminescence imaging, which harnesses the light-emitting properties of enzymes such as luciferase for quantification of cells and uses low-light imaging systems. This strategy could be useful for the study of a wide range of biological processes, such as the pathophysiology of graft-versus-host and graft-versus-leukaemia reactions.

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Figure 1: Schematic representation of a bioluminescence imaging strategy using cells from a transgenic donor mouse.
Figure 2: Sensitivity of detection in bioluminescence imaging studies.
Figure 3: Imaging of graft-versus-host disease.
Figure 4: Effect of transfer of conventional CD4+ and CD8+ T cells with and without CD4+CD25+ regulatory T cells on tumour progression.

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Authors and Affiliations

  1. the Departments of Medicine, Center for Clinical Research Building, 269 West Campus Drive and Pediatrics, Clark Center, 318 Campus Drive, Stanford University, Stanford, 94305, California, USA

    Robert S. Negrin & Christopher H. Contag

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  1. Robert S. Negrin
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Correspondence to Robert S. Negrin.

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C.H.C. is a founder and consultant for Xenogen, Alameda, California, USA.

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Glossary

Allorecognition

Allorecognition occurs when the host immune system detects same-species, non-self antigens and triggers allograft rejection. It can occur by direct or indirect pathways: the direct pathway involves recognition of foreign MHC molecules on donor cells, and the indirect pathway involves processing and presentation of donor-derived MHC molecules by host antigen-presenting cells.

Graft-versus-host disease

(GVHD). Tissue damage in a recipient of allogeneic tissue (usually a bone-marrow transplant) that results from the activity of donor cytotoxic T cells recognizing the tissues of the recipient as foreign. GVHD varies markedly in extent, but it can be life threatening in severe cases. Damage to the liver, skin and gut mucosae are common clinical manifestations.

Graft versus leukaemia

Hosts with leukaemia who receive an allogeneic bone-marrow transplant have far fewer disease relapses than individuals who obtain autologous bone-marrow transplants. This results from the transplanted T cells recognizing alloantigens expressed by the leukaemia.

Haematopoiesis

The commitment and differentiation processes that lead from a haematopoietic stem cell to the production of mature cells of all lineages: erythrocytes, myeloid cells (such as macrophages, mast cells, neutrophils and eosinophils), B and T cells, and natural killer cells.

Minor histocompatibility antigens

Polymorphic peptides derived from normal cellular proteins that can be recognized in the context of MHC molecules. Immune responses to these polymorphic antigens can result in graft-versus-host reactions, graft rejection or beneficial antitumour responses.

Non-myeloablative haematopoietic-cell transplantation

An allogeneic haematopoietic-cell transplantation in a recipient who has received a conditioning regimen to achieve immunosuppression and prevent graft rejection without the complete ablation of host haematopoiesis. The recipient might develop (transient) mixed chimerism, owing to haematopoietic recovery of the host and engraftment of donor haematopoietic cells.

Two-photon intravital microscopy

Laser-scanning microscopy that uses pulsed infrared laser light for the excitation of conventional fluorophores or fluorescent proteins. The main advantage is deep tissue penetration of the infrared light, owing to the low level of light scattering in the tissue.

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Negrin, R., Contag, C. In vivo imaging using bioluminescence: a tool for probing graft-versus-host disease. Nat Rev Immunol 6, 484–490 (2006). https://doi.org/10.1038/nri1879

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