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.

The Efficacy of Prepared Specific Pseudomonas aeruginosa Transfer Factor to Protect Mice against Experimental Challenge

“…Meanwhile, the most important restriction related to the transfer of the T-cell from the donor to the recipient is the graft-versus-host reaction which occurred due to the immune-mediated attack of recipient tissue by the donor T cells (Schroeder, 2002;Ferrara et al, 2010;Schroeder and DiPersio, 2011), to avoid this reaction, Munster et al (1974) suggested the use of transfer factor or xenogeneic cells in adoptive transfer of the cellular immunity. The TF is non-antigenic, and did not stimulate any immune reaction in the recipients due to its small molecule size, in contrary to the viable T cells (Kirkpatrick, 1996).…”

Unique patterns of CD8+ T-cell-mediated organ damage in the Act-mOVA/OT-I model of acute graft-versus-host disease

“…hours apart) and on the same day (aHSCT + Day 0), within 6 hours, grafted with donor-derived 3x10 6 bone marrow cells and 1,5x10 7 splenocytes via retro-orbital infusion [23], thus resembling typical setups used in most standard murine aGVHD models [8]. In our hands, this approach, hereafter termed as the OT-I → Act-mOVA aGvHD model, induced well known hallmarks of mouse GvHD in recipient animals such as diarrhea, hunchback, ruffled fur and apathy.…”

“…Currently, the most frequently used murine models of human aGvHD utilize distinct, inbred mouse strains as allogenic donors and recipients to induce aGvHD upon experimental aHSCT [6][7][8]. This approach is highly efficient, as it achieves both major and minor allele disparities between donor and recipient, and evokes potent aGvHD mediated by graft CD8+ T cells, CD4+ T cells, or both [9,10].…”

Pharmacogenomics Dictate Pharmacokinetics: Polymorphisms in Drug-Metabolizing Enzymes and Drug-Transporters

“…2011). Several disease specific knockout and transgenic mouse models are also used, for instance, to study cardiovascular drugs (Avila MD, 2011;Xiangdong L, 2011;Zaragoza C, 2011) and autoimmune disease targeting agents (Gulinello M, 2011;Schroeder MA, 2011). Immunodeficient animals, such as nude, SCID and SCID/NOD tumor xenograft mouse models, are also important for testing and development of new chemotherapeutic drugs (Sausville EA, 2006;Khan N, 2009;Umar A, 2010;Baiocchi M, 2010).…”