Mouse models of bone marrow transplantation

Area of Science:

• Immunology
• Hematology
• Transplantation Biology

Background:

• Mouse models have been pivotal in elucidating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) mechanisms over 50 years.
• Key insights include the T cell dependency of GVHD and GVL, and the role of inflammatory cytokines in GVHD pathogenesis.

Purpose of the Study:

• To review the historical and ongoing contributions of mouse models to understanding GVHD and GVL.
• To highlight emerging concepts in GVHD mediated by antigen-presenting cells and T cell subsets.
• To discuss the utility of mouse models for preclinical research in transplantation.

Main Methods:

• Utilizing mouse models of bone marrow transplantation.
• Employing knockout and transgenic approaches to dissect GVHD and GVL mechanisms.
• Applying "real-time" immunologic imaging techniques to study GVHD and GVL in vivo.

Main Results:

• Mouse models have consistently validated clinical observations regarding T cell-mediated GVHD and GVL.
• Recent findings from mouse models emphasize the impact of inflammatory cytokines on GVHD.
• New concepts regarding antigen-presenting cell and T cell subset roles in GVHD are emerging from preclinical studies.

Conclusions:

• Mouse models remain the predominant preclinical platform for dissecting GVHD and GVL.
• Continued research using these models, incorporating advanced imaging, promises significant clinical advances in transplantation therapy.
• Understanding the interplay of immune cells and cytokines is key to improving transplant outcomes.