Mouse models of graft-versus-host disease: advances and limitations

Abstract

The limiting factor for successful hematopoietic stem cell transplantation (HSCT) is graft-versus-host disease (GvHD), a post-transplant disorder that results from immune-mediated attack of recipient tissue by donor T cells contained in the transplant. Mouse models of GvHD have provided important insights into the pathophysiology of this disease, which have helped to improve the success rate of HSCT in humans. The kinetics with which GvHD develops distinguishes acute from chronic GvHD, and it is clear from studies of mouse models of GvHD (and studies of human HSCT) that the pathophysiology of these two forms is also distinct. Mouse models also further the basic understanding of the immunological responses involved in GvHD pathology, such as antigen recognition and presentation, the involvement of the thymus and immune reconstitution after transplantation. In this Perspective, we provide an overview of currently available mouse models of acute and chronic GvHD, highlighting their benefits and limitations, and discuss research and clinical opportunities for the future.

Fig. 1.

Steps to aGvHD in mice. The progression of events occurring in the development of aGvHD in the mouse is illustrated. The five crucial steps of immune priming (A), activation (B), T-cell expansion (C), T-cell trafficking (D) and host tissue injury (E) are outlined. DC, dendritic cell; XRT, radiation conditioning. See main text for full details.

Fig. 2.

Steps to cGvHD in mice. The progression of events occurring in the development of cGvHD in the mouse is illustrated. The five steps illustrate immune priming (A), activation of T and B cells (B), T-cell expansion and B-cell autoantibody production (C), trafficking to sites of tissue damage (D), and end organ damage through chronic inflammation and fibrosis (E). See main text for full details.