Self and non-self recognition in Xenopus laevis
Description
The process by which Xenopus laevis acquire the ability to distinguish self from non-self was investigated by allografting and thymectomy Self recognition was investigated by studying certain of the conditions which promote tolerance to histocompatibility antigens expressed on transplanted donor allogeneic tissue. Tolerance was induced by transplanting whole eyes unilaterally between larvae at stages 31 through 49. After metamorphosis, test skin allografts were placed on the eye recipients. It was seen that if the eye graft was maintained, tolerance was induced to the alloantigens expressed on the donor tissue, and the test grafts were accepted. In 7 of 12 animals which failed to maintain the transplanted eye, test grafts were not accepted. The grafted eyes of some animals were experimentally removed to determine the effect on tolerance, and in one case, breakdown of tolerance was observed. Tolerance was transferred passively to naive immunocompetent hosts by means of thymus implants from tolerant donors at stage 50-53. Spleen implants and serum from tolerant donors was not successful in conferring tolerance, however. A requirement for persistence of the tolerizing antigen through metamorphosis for tolerance maintenance was observed. The results were consistent with a mechanism of active suppression operative in tolerance induction and maintenance The development of alloreactivity of non-self specificities was investigated by studying the effect of very early thymectomy on first, second and subsequent allograft responses. Prolonged first set allograft survival was seen in animals that had been thymectomized at larval stages 41-49. However, thymectomy at progressively earlier stages resulted in a larger and larger proportion of animals unable to reject second set grafts. In some animals, the allograft response remained deficient even after multiple challenges. The results indicate that the thymus processes T-cells starting upon its formation and that these cells which are competent to respond to alloantigens not present in the embryo are released to the periphery almost immediately It is proposed that the acquisition of tolerance to self is a property acquired by precursor T-cells at the periphery as they migrate to the thymus via a circulatory route. Since tolerance can be induced until stage 48, and immigration of precursor cells to the thymus continues from stage 41 until at least stage 49-50, it is concluded that late arriving precursor T-cells, tolerized to foreign antigen between stages 41-48, are effective in actively suppressing the alloreative cells previously processed and released by the thymus