INCOMPLETE TOLERANCE INDUCED IN XENOPUS BY LARVAL TISSUE ALLOGRAFTING- EVIDENCE FROM IMMUNOHISTOLOGY AND MIXED LEUKOCYTE-CULTURE

Application of adult skin allografts to Xenopus larvae has been a favo ured protocol for probing the development of self-tolerance. A more ph ysiologic approach is presented here that examines the immunologic out come of grafting semi- or fully allogeneic larval skin or spleen to ag e-matched, larval Xenopus (X. laevis/X. gilli clonal hybrids). Followi ng such grafting at 2 or 4 weeks-of-age, young froglets (4-5-months-ol d) are generally unable to reject second-set skin transplants, but des troy third-party skin vigorously, the MHC class 11-rich spleen proving especially effective at inducing this tolerance. In contrast, followi ng larval grafting of semiallogeneic tissues, mixed leucocyte culture performed at the end of metamorphosis (6 weeks) and again at 6 months reveals splenocyte reactivity toward donor-strain stimulators. Immunoh istological findings extend this observation of anti-donor reactivity (suggesting incomplete tolerance) to the graft site. Thus despite exce llent health when viewed externally, apparently tolerated second-set s kin transplants display localised infiltration (especially into the ep idermis) by CD8+ T cells and increased numbers of MHC class I and II-e xpressing cells by 3 weeks post-grafting. The immunologic implications of these findings are discussed.