Comparative Study of Skin Graft Tolerance and Rejection in the Frog Xenopus Laevis

Over the last few decades, the amphibian Xenopus laevis1 has been used as a unique comparative model to study the developmental and immunological aspects of tissue transplantation as well as self tolerance (Du Pasquier, Schwager et al. 1989; Robert and Ohta 2009). The immune system of X. laevis, one of the best defined outside mammals and chickens, is fundamentally similar to that of mammals. Notably, the evolutionary distance of X. laevis from mammals permits distinguishing species-specific adaptations from more conserved features of the immune system. In addition, advanced genetic resources including the full genome sequence of the X. leavis sister species X. tropicalis, a large collection of EST, cDNA and genomic (BAC, Fosmid) libraries for both species, efficient transgenesis and genome wide mutagenesis has markedly empowered X. laevis as a biomedical model. Furthermore, several different major histocompatability complex (MHC) defined inbred strains of X. laevis, as well as clones sharing identical MHC haplotypes but differing at multiple minor histocompatibility (H) loci, provide a unique opportunity to study T cell regulation in vivo by skin graft. More information about these resources can be found on the Xenbase website (http://www.xenbase.org/common/) (Bowes, Snyder et al. 2009) and the X. laevis research resource for immunobiology (http://www.urmc.rochester.edu/mbi/resources/Xenopus/) (Robert 2006). The objectives of this review are first to provide short background information on the immune system and skin graft biology in X. laevis, and then to examine the use of the minor H-Antigen (Ag)-disparate skin grafting model system in X. laevis isogenic clones and to investigate in vivo the immunostimulatory properties of certain heat shock proteins (hsps) such as gp96 and hsp70 with particular emphasis on minor H-Ag specific T cell responses. We will also consider the possible role of nonclassical MHC class Ib molecules in this context. Furthermore, we will re-evaluate old data on induction of long term immunological memory and immune tolerance in X. laevis larvae to skin graft Ags in the context of immune regulation. Finally, we will discuss the possibility to use hsps and new genetic tools