Induction of skin allograft tolerance during metamorphosis of the toad xenopus laevis: a possible model for studying generation of self tolerance to histocompatibility antigens

Abstract

From 15 days before to 60 days after metamorphosis, an immunologically specific tolerance to skin allografts between individuals of Xenopus can be induced by skin allografts. Genetic inheritance of histocompatibility antigens determines the degree of tolerance during metamorphosis: in individuals from the first generation, 25-50 % of the siblings were tolerant. In second generation individuals, the percentage of tolerance is 75-100 % when the parents show mutual tolerance to skin allografts at metamorphosis and only 25 % when the parents are mutually incompatible. In view of the characteristics of this tolerance it is suggested that it concerns mainly weak histocompatibility antigens and that it occurs preferentially at metamorphosis, as at this stage the animal becomes tolerant to many new self-antigens.

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

“…Skin graft rejection is a well-established technique in X. laevis that has been used for determining the segregation of both major and minor H-Ag loci (Chardonnens and Du Pasquier 1973;Du Pasquier and Bernard 1980;Ramanayake, Simon et al 2007). The entire graft appears silvery due to the presence of irridophores.…”

“…We have recently described this technique in details (Nedelkovska, Cruz-Luna et al 2010 (abdominal skin which appears silvery due to the presence of irridophores) and inserting it under the dorsal skin of the recipient (Chardonnens and Du Pasquier 1973;Nedelkovska, Cruz-Luna et al 2010). It is critical to handle the graft gently and avoid damage with the forceps, which would obscure the results.…”

“…For this reason, the use of ventral adult, instead of larval skin, graft onto larval recipients has been and is still favored. The adult skin is introduced under the larval skin on the head between the ears of the recipient (Chardonnens and Du Pasquier 1973). Another difference is that compared to adults, larvae are transparent.…”

“…laevis tadpoles develop allorecognition at stage 49 (12 days post fertilization) which is accompanied by lymphocytic infiltration of the grafts (Horton 1969). In X. laevis there are three distinct periods throughout development during which there is a difference in the immune responses against skin allografts (Chardonnens and Du Pasquier 1973). Those include the periods before, during and after metamorphosis.…”

Tolerance Induction in Thymectomized, Adult Xenopus by Co-Transplantation of Thymus and Tolerated Skin Graft

“…Xenopus serves as a model for studying self-tolerance. Allogeneic or semi-xenogeneic adult skin grafts readily tolerize perimetamorphic Xenopus larvae (Chardonnens and Du Pasquier, 1973;DiMarzo and Cohen, 1982a, b;Tochinai, 1993), whereas skin grafts of the same genetic combinations transplanted to adults are always rejected. Since splenic lymphocytes obtained from animals that tolerated skin grafts retain their proliferative responsiveness to the skin donor antigens both in vitro and in vivo (Flajnik et al, 1985;Arnall and Horton, 1987;Sakuraoka and Tochinai, 1993), and since tolerance is barely inducible in metamorphosing larvae that have been thymectomized just before skin grafting (Barlow and Cohen, 1983;Tochinai, 1993), it is thought that tolerance induction in Xenopus larvae may result from a thymusderived suppressive activity rather than from clonal deletion or anergy of immunocompetent T cells.…”