PROLONGED SURVIVAL OF MAJOR HISTOCOMPATIBILITY COMPLEX-DISPARATE SKIN ALLOGRAFTS TRANSPLANTED TO THE METAMORPHOSING FROG, XENOPUS LAEVIS

Abstract

Perimetamorphic larval and postmetamorphic froglet X. laevis were grafted with adult skin which differed from the host by 1 or 2 major histocompatibility complex (MHC) haplotypes and multiple minor H loci. In family studies, long-term survival of 1 MHC haplotype-disparate grafts was observed at frequencies from 10-100% when perimetamorphic F1 progeny were grafted with skin from their field-collected, presumably MHC heterozygous parents. When donor and host differed by 2 MHC haplotypes, fewer metamorphosing recipients retained intact grafts. Recipients transplanted with 1st-set grafts as postmetamorphic froglets rejected their transplants in all protocols. Rejection of 1- or 2-MHC haplotype-disparate allografts by animals grafted during the perimetamorphic period was chronic and variable; skin graft rejection by animals grafted after metamorphosis was more acute. Studies using partially inbred strains of Xenopus, whose MHC haplotypes are genetically defined, confirmed results from family studies. The incidence of allograft survival on perimetamorphic recipients was 93% when donor and host differed by 1 MHC haplotype and 30% when transplantation was across a 2-HMC haplotype barrier. Animals in 1 family that were 1st-set grafted during metamorphosis and did not completely reject their grafts during the > 2 yr that they were observed promptly rejected 3rd-party grafts that were transplanted 28 mo. after the initial transplantation procedure. Changes in the animals'' lymphoid and endocrine systems are known to occur at metamorphosis. Acceptance of allografts by animals grafted during metamorphosis may reflect their physiological changes or it may be a byproduct of immunological mechanisms necessary for self-tolerance that have been postulated to be present at this time in development.