The role of the regional lymph node in the response to secondarily vascularized grafts

Studies using neonatal hearts grafted into the foot pads of adult rats have shown significant differences in the tempo of rejection in various RT1-incompatible combinations of donor and recipient rats. The model allows simultaneous study of events in the graft and in the regional node draining the graft. Removal of the regional node in the inductive stages of the immune response resulted in highly significant prolongation of graft survival. This effect was not due to lymphatic interruption per se or to clonal deletion. The effect was independent of the presence of the primary graft. Second grafts implanted in animals from which both the original graft and its regional node had been removed showed prolonged survival. Once survival of the original graft, from which the node was removed, was established, survival of second grafts bearing the same antigens was also prolonged, although third-party grafts were rejected in first set time. The data suggest that the microenvironment and anatomical connections of the lymph node that first receives antigen, or the cells that have contacted antigen in the graft, or both, play a vital role in an orderly sequence of cellular interaction and migration that culminates in graft rejection. Interruption of this sequence by node removal appears to divert the alloimmune response toward specific enhancement of the graft.