THYMUS-MEDIATED TOLERANCE TO CELLULAR ALLOANTIGENS

Abstract

The role of the thymus as a possible site of induction and maintenance of specific immune tolerance to eel- lular alloantigens was investigated. Sublethally irradiated mice can be made tolerant by an injection of H-3 incompatible spleen cells into or outside the thymus. When the inoculum was given extra-thymically, dividing donor cells penetrate into the thymus if the recipient was either newborn or sublethally irradiated when adult. A direct inoculation into the thymus is not required for an intrathymic action of antigen in tolerance induction in the case of those cellular antigens which seem to possess a natural vehicle. Strain A mice were lethally irradiated and induced to recovery by infusion of syn-geneic fetal liver cells. The immature lymphoid cells from the curative inoculum are thymus-dependent and tolerance-responsive. The recipients'' thymus was replaced by a syngeneic, but presumably CBA cell-containing thymus (from donors tolerant to CBA antigens) or by a semiallogeneic thymus (from (A x CBA)Fi hybrids). In both cases, the implanted thymus was the only source of CBA antigens for the induction of tolerance in the fetal cells. Where the "tolerant" thymuses were implanted subcutaneously to the radiation chimeras, only prolonged survival of CBA skin grafts resulted. The implantation of F1 hybrid thymuses under the kidney capsule resulted in a high degree of permanent tolerance (lasting for more than 150 days). Transfer of hybrid lymph nodes to nonthymectomized but splenec-tomized chimeras resulted in only temporary tolerance, while the effect of hybrid spleen was comparable to that of the thymus. A possible explanation of these findings based on a thymus-mediated mechanism of tolerance to cellular alloantigens is suggested.