Impaired rejection of minor-histocompatibility-antigen-disparate skin grafts and acquisition of tolerance to thymus donor antigens in allothymus-implanted, thymectomized Xenopus.

We examine whether J strain Xenopus laevis and X laevis/gilli (LG) isogeneic hybrids, thymectomized (Tx) at 7 days and implanted with larval or postmetamorphic thymus (either normal or irradiated) in late larval life, can be used to explore the role of the developing thymus in the education of minor histocompatibility (H) antigen-reactive T cells and in the acquisition of tolerance to MHC (major histocompatibility complex) antigens. Tx LG Xenopus implanted with isogeneic thymus display fully restored ability to reject both MHC-incompatible and minor H-disparate grafts. Allothymuses (both MHC- and minor-H-disparate) restore normal rejection of skin grafts with MHC incompatibility to thymus donor and Tx (J or LG) host, but reactivity to grafts with putative minor H disparity is impaired. Defective minor-H-disparate skin graft rejection occurs even when the Tx host has received a thymus of the "correct" MHC haplotype (i.e., the same MHC as the assay skin graft). This defect may be attributable to inadequate establishment of minor-H-reactive T lymphocytes, to sharing of minor antigens, or to "nonspecificity" of tolerance induction to minor antigens, since such tolerance is demonstrated here following perimetamorphic grafting of skin to control LG clones. Skin grafts from Xenopus isogeneic to the donors of the MHC-incompatible larval and adult thymus implants are always tolerated by Tx hosts. In contrast, in vitro one-way MLC (mixed leukocyte culture) reactivity of splenocytes to thymus donor MHC antigens occurs when certain donor/host combinations are used but not when others are tested. Postmetamorphic thymus implants appear to promote in vitro MLC tolerance more effectively than larval thymus implants.