Induction of donor-specific tolerance to rat cardiac allografts by intrathymic inoculation of bone marrow.

Abstract

Induction of donor-specific tolerance to tissue or organ allografts can readily be achieved by administration of allogeneic bone marrow to neonatal rodents; however, in adult recipients induction of transplantation tolerance by this strategy generally requires intensive cytoablative conditioning. Described here is a novel method of promoting transplantation tolerance that involves inoculation of donor bone marrow into the thymus of transiently immunosuppressed adult recipients. Prospective Wistar-Furth recipients were inoculated with allogeneic Lewis bone marrow cells (BMCs) either intrathymically or intravenously in conjunction with a single dose of antilymphocyte serum 2 to 3 weeks before receiving donor-strain cardiac allografts. Recipients were monitored for graft survival and examined for presence of hematopoietic chimerism. Intrathymic but not intravenous inoculation of donor BMCs led to permanent survival of donor-strain cardiac allografts, whereas third-party Dark agouti cardiac allografts were rejected promptly. Persistence of donor chimerism was demonstrated in the thymus of Wistar-Furth recipients of intrathymic Lewis BMCs for as long as 3 weeks after BMC inoculation. Intrathymic inoculation of BMCs concurrently with a single dose of antilymphocyte serum induces donor-specific unresponsiveness to rat cardiac allografts. The unresponsiveness may be the result of deletion or functional inactivation of alloreactive clones maturing in a thymus bearing donor alloantigen. Intrathymic inoculation of BMCs deserves further evaluation as a possible clinical strategy for the induction of transplantation tolerance.