The mechanism by which the antigen-specific immune system distinguishes between
foreign antigens (toward which it mounts an immune response) and self-antigens (of
which it is tolerant) is not completely understood. Studies using “superantigens” and
transgenic mice have allowed investigations into some of the mechanisms of clonal
deletion, anergy, and peripheral tolerance. In the present report, we have attempted to
develop a new model system to investigate the possible mechanism(s) of peripheral
tolerance to allografts. In this system, skin grafts from C57BL/6J (B6; H-2b mice are
grafted onto T- and B-lymphocyte-deficient C.B-17-scid/scid (H-2d; hereafter referred to
as scid) mice. Because of their lack of functional lymphocytes, the scid mice readily
accept the allogeneic skin grafts. After the allografts healed, the scid mice were
reconstituted with T-cell-deficient fetal liver from coisogeneic C.B-17-∤/∤ mice or bone
marrow from weanling congenitally athymic BALB/c-nu/nu (H-2d; hereafter referred to
as nude) mice. Upon immunological reconstitution, the scid mice reiected the established
B6 skin allografts, suggesting that an immune system developing in the presence of an
intact peripheral skin allograft fails to develop tolerance to the peripheral allograft. This
model system may be useful for the study of the mechanisms required for the induction
of peripheral tolerance.