June 1, 2009;
Comparative and developmental study of the immune system in Xenopus.
Xenopus laevis is the model of choice for evolutionary, comparative, and developmental studies of immunity, and invaluable research tools including MHC
-defined clones, inbred strains, cell lines, and monoclonal antibodies are available for these studies. Recent efforts to use Silurana (Xenopus) tropicalis for genetic analyses have led to the sequencing of the whole genome. Ongoing genome mapping and mutagenesis studies will provide a new dimension to the study of immunity. Here we review what is known about the immune system
of X. laevis integrated with available genomic information from S. tropicalis. This review provides compelling evidence for the high degree of similarity and evolutionary conservation between Xenopus and mammalian immune systems. We propose to build a powerful and innovative comparative biomedical model based on modern genetic technologies that takes take advantage of X. laevis and S. tropicalis, as well as the whole Xenopus genus. Developmental Dynamics 238:1249-1270, 2009. (c) 2009 Wiley-Liss, Inc.
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Fig. 1. Schematic overview of the Xenopus tumor/minor H-Ag transplantation system. Several syngeneic clones produced gynogenetically from X. laevis × X. gilli hybrids have been MHC typed. While some have different MHC haplotypes (e.g., LG-3 [b/d]) and LG6 [a/c]), others share the same MHC haplotype but express different minor H-loci (LG-6 and LG-15). On the left side, skin grafts exchanged among individuals of the same LG-15 isogenetic clone are not rejected (top), whereas skin grafts on individuals of the LG-6 clone that is MHC identical with LG-15 but differs at minor H-loci are rejected significantly more slowly (middle) than are MHC-disparate allografts (bottom). On the right side, the 15/0 tumor is tumorigenic when transplanted in the clone from which it derives (LG-15, top), as well as MHC identical but minor H-Ag–disparate LG-6 clone, but is rejected in the MHC-disparate LG-3 host. For abbreviations, see list.
Fig. 2. Schematic overview of a typical mammalian adaptive immune response. Productive T-cell activation requires two signals from an APC (e.g., dendritic cells, macrophages): the first signal is due to the recognition by the TCR of the MHC molecules complexed with the antigenic peptide (CD4 T cells interact with class II molecules, CD8 T cells with class I molecules), the second signal is provided by costimulatory molecules (e.g., B-7, CD40) that are up-regulated following APC activation by pathogen products or PAMPs binding to PRRs such as TLRs. Activated T cells proliferate and differentiate into cell effectors: CTLs able to kill target expressing the same Ags-class I complex and CD4 T helper cells producing various cytokines that act on the pathogen as well as on other immune cells including CD8 T and B cells. Most T cells die from apoptosis after the response (contraction phase), except a long-lived minor population of memory T cells able to respond faster to a second pathogen exposure. For abbreviations, see list. [APC= antigen presenting cell; Ag =Antigen]
Schematic overview summarizing the major developmental steps of the Xenopus immune system. For abbreviations, see list. [DNP=dinitrophenol; GALT=gut-associated lymphoid tissue; H-ag =histocompatibility antigen; Ig=immunoglobulin; MHC=major histocompatibility complex; MLR=mixed lymphocyte reaction; NK cells=natural killer cells; TCR=T-cell receptor]