IMMUNOLOGICAL TOLERANCE IN THE AMPHIBIAN XENOPUS LAEVIS (DAUDIN)

Abstract

Observation of some of the phenomena of tolerance to soluble protein antigens and allogeneic tissue transplants in Xenopus laevis has formed the framework of the present study. The method of larval induction of high-zone tolerance used in this laboratory has been confirmed and further analysed. Larvae treated with high doses of Human-γ-globulin (HGG) were unable to produce anti-HGG antibody after challenge. The proliferative response demonstrated in the spleens of tolerant toadlets 21 days after challenge was, however, of similar magnitude to that in normally responding animals. Adoptive transfer of high-zone tolerance specific to HGG was demonstrated by intravenous inoculation of tolerant histocompatible splenocytes simultaneously with an antigenic challenge via the dorsal lymph sac. This is indicative of the active involvement of a suppressor T-cell population. The induction of high-zone tolerance in X. laevis results in changes in spleen cell populations as demonstrated by buoyant density gradient separation. Spleen cell sub-populations taken from the separated layers were not, however, effective in the adoptive transfer of tolerance. A normal lymphocyte transfer reaction was observed in X. laevis to show a number of characteristics seen in the mammalian reaction. The use of mitomycin-C treated donor cells and early thymectomized hosts has demonstrated that the phenomenon is composed of donor and host components which are largely distinct from each other. Implantation of allogeneic larval spleens resulted in the induction of transplantation tolerance or impaired rejection in a significant proportion of skin grafted toadlets in which both the donor and host larvae were up to and including stage 51 at the time of transplantation. The implication of these results is that immunomaturity of the donor and host is important in the induction of transplantation tolerance but that other factors must also be involved.