Analysis of neonatally induced tolerance of H-2 alloantigens. IV. Graft adaptation in long-term tolerated grafts.

Acceptance of orthotopic test skin grafts bearing putative tolerogenic H-2 determinants proves to be the most stringent criterion for the existence of neonatally induced transplantation tolerance. The large majority of long-standing grafts retain their original antigenicity--that is, they are rejected when tolerance is abolished by infusions of immunocompetent cells syngeneic with the tolerant host; and they remain immunogenic--that is, they induce their own rejection when excised and placed on naive recipients syngeneic with the tolerant animal. However, the ability of these long-standing grafts to reflect concordantly the alloreactive potential of peripheral lymphoid cells of tolerant mice deteriorates in time. A minority of tolerated grafts lose their ability to express their genetic endowment of H-2 alloantigens in an immunogenic form through a process of graft adaptation. Because the majority of long-standing Ia-disparate grafts remain immunogenic when transplanted to naive recipients, the adaptation process can not be ascribed exclusively to repopulation of original epidermal Langerhan's cells with similar cells of host origin.