Neonatal Grafts Research Articles

SPECIFIC AND NON‐SPECIFIC COMPONENTS IN THE EFFECT OF HISTOCOMPATIBILITY ANTIGENS IN NEONATAL SKIN GRAFTS ON THE HOST'S IMMUNE RESPONSE CAPACITY

SUMMARYThe‘tolerogenicity’of neonatal skin grafts, as reflected in their higher survival rate as well as in their capacity to confer this tendency upon simultaneous adult grafts, has been believed to be based on an immunologically specific feature of the neonatal alloantigens.The data presented in this study demonstrate in two weak histocompatibility systems (H‐9 and that presented by the male‐specific antigen, MSA) that there is also an important non‐specific component in the tolerogenic mechanism of neonatal skin allografts. The survival of adult skin allografts was followed in double‐grafted animals in which the neonatal graft was either a specific or non‐specific allograft or a syngeneic graft. Although the maximum increase in the survival rate of the adult grafts (in comparison to single‐grafted controls) was induced by antigenically specific neonatal grafts, significant effects were also induced by antigenically neutral (syngeneic) or antigenically non‐specific neonatal grafts. The immunologically nonspecific component in the effect of neonatal skin grafts could be traced back to their primarily high contents of proteoglycans and to their long‐lasting production of the latter; consequently, the neonatal graft which is protected by these substances against the concomitant round cell infiltration can secondarily provide some protection also to the adult allograft. This non‐specific protection may favour a stepwise establishment of a specific tolerance.

Skin homografts: tolerogenic versus immunogenic influences in mice.

In strain combinations involving multiple non-H-2 disparities, neonatal skin grafts may survive significantly longer than adult grafts of similar genotype on normal adult hosts, and repeatedly outlive grafts of adult origin on immunosuppressed recipients. Moreover, newborn grafts of long-standing may render their hosts unresponsive to adult skin grafts from the same donor strain. With some H-2-compatible strain combinations in which homozygous neonatal grafts are rejected, F(1) hybrid (heterozygous) grafts of similar age not only may survive indefinitely, but also may induce tolerance of subsequent adult parental strain homografts. These tolerogenic and gene dosage effects, although much weaker, can likewise be revealed with H-2-incompatible neonatal skin grafts.