Continuous alloantigen elimination--a concept for allograft tolerancer

The "enhancement" phenomenon evoked in rats by administration of donor lymphocytes and recipient-anti-donor-lymphocyte antibodies prior to organ transplantation brings about "continuous alloantigen elimination". This new concept is based on the experimental data from studies on the distribution of radiolabelled alloantigen and alloantibody in the recipient lymphoid organs and suggests that immediately after organ transplantation to the "enhanced" recipient, the circulating antibodies bind to the donor transplantation antigens both on endothelial cells and those shed into recipient blood circulation. The formed alloantigen-alloantibody complexes are trapped in the spleen and after opsonization and binding to the migrating splenocytes are transported to the liver for further processing. The process of continuous binding of alloantigen and elimination as alloantibody-alloantigen complexes in the lymphoid organs of the recipient prevents activation of the recipient effector cells and their migration to the graft. The organ grafts survive above 100 days. Although there is no evident rejection in the allograft itself a phenomenon of "rejection alert" is seen in the lymphoid tissue. The lymphocytes originating from the organ graft donor injected intravenously are rejected in the "enhanced" recipient spleen and nodes within 6 hours. The "physiological" site of elimination (rejection) of alloantigens are the lymphoid organs, as it happens with invading pathogens. The allotransplant is spared since its alloantigens are "blocked" by anti-donor-specific antibodies, the complexes are continuously detached and washed-off by the percolating blood and eliminated in the lymphoid tissues and liver.