INTRATHYMIC ADMINISTRATION OF B-CELLS INDUCES PROLONGED SURVIVAL OF FULLY ALLOGENEIC CARDIAC GRAFTS WITHOUT PROLONGED DELETION OF DONOR-SPECIFIC THYMOCYTES

Intrathymic (IT) injection of alloantigen has been shown to induce unr esponsiveness to allografts although the exact mechanisms of tolerance induction remains unclear. C57BL/10 (H2(b)) cardiac allografts were a ccepted in C3H/He (H2(k)) mice pretreated with IT inoculation of donor splenocytes (1 x 10(6)) in combination with a depleting anti-CD4 mono clonal antibody 27 days before cardiac transplantation. To investigate which cell types were responsible for tolerance induction by IT injec tion of alloantigen, resting B (rB) cells or dendritic cells were used as the thymic inoculum instead of whole splenocytes. IT injection of rB cells induced indefinite graft prolongation in all recipients while only 20% of mice that had received IT injection of dendritic cells ac cepted grafts for over 100 days. In contrast, IT injection of dendriti c cells resulted in significant deletion of donor-specific thymocytes whereas rB cells were relatively ineffective. IT deletion is not essen tial for the induction of tolerance by IT injection of rB cells; nonde letional mechanisms can be involved.