Evidence that a similar range of alloimmune responses can develop in murine and human allograft recipients

Based on discrepancies between various laboratory and clinical observations, skepticism has developed regarding the pre-clinical value of rodent immunologic studies. In this article, we review the progression of our murine and human studies over the last several years, which have demonstrated that humans and mice can make very similar types of immune responses in vivo to allografts. Early studies by ourselves and others, demonstrated that mice can make either pro-inflammatory (rejection) or anti-inflammatory (acceptance) immune responses to graft alloantigens. We demonstrated that donor-reactive DTH assays could be used to monitor which type of alloimmune response had been selected by the allograft recipient. To help determine if similar immune response options are available to humans and detectable by DTH assays, we first developed the transvivo DTH assay. In this system, mice are used as a receptacle in which DTH responses made by human PBMC can be induced and measured. These transvivo DTH studies revealed that human allograft recipients, like mice, commonly make either pro-inflammatory or anti-inflammatory immune responses to graft alloantigens. In transplant patients, this rarely correlates with the development of donor-reactive alloantibodies during the post-transplant period.