Successful induction of specific hyporeactivity to rat skin xenografts in newborn mice. Effect of immunoregulatory molecules.

Inoculation of newborn mice with spleen and bone marrow cells from newborn (less than 24-hr-old) rat donors, as compared with cells from adult donors, resulted in induction of profound hyporeactivity or even long-lasting tolerance of skin xenografts. This tolerance was specific since skin allografts transplanted to tolerized mice simultaneously with specific rat grafts were rejected in normal fashion. Analysis of the reactivity in vitro in mixed lymphocyte culture and cytotoxicity assays revealed that cells from tolerant animals were specifically nonreactive to the tolerated xenogeneic antigens. Administration of active supernatants from cultures of concanavalin A-stimulated spleen cells from adult rats to tolerized mice within the first 5 days after birth impaired tolerance. The results show that the approach used is the first successful model of neonatal induction of tolerance to skin xenografts in mammals and emphasize the role of immunoregulatory factors in this process.