I. Renal allografts will be investigated in genetically pedigreed dogs in order to assess the role of antibodies to antigens encoded by non-MHC genes in hyperacute rejection. Human material will be studied to develop cross-match procedures which will permit avoiding hyperacute rejection in a more reliable way than the present procedures. II. Immune complexes playing a role in pathogenicity of renal diseases and in destruction of renal grafts will be studied with the specific aim of identifying the antigen(s) responsible for the complex formation. Primarily, a procedure of dispersion of complexes in the excess of the putative antigen will be employed. III. Various humoral antibodies that appear in human recipients of renal grafts will be studied with the aim of assessing their role in the graft rejection and of ascertaining their value in recognizing the impending graft rejection. These studies will include the previously described heterophile transplantation antibodies, as well as other allo- and panantibodies discovered in this laboratory. IV. Bone marrow transplantation will be performed i rhesus monkeys exposed to total body irradiation. Allogeneic marrow will be conditioned in such a way that it will repopulate the irradiated monkey without causing GvH reaction. This will be achieved by incubating the marrow in rabbit anti-human lymphocyte serum which will be properly absorbed in order to destroy lymphocytes, but not primitive hemopoietic cells. This study will be, hopefully, of significance for clinical bone marrow transplantation. V. Studies on xenografts will be conducted with the final objective of obtaining soluble preparations from xenogeneic tissues which will neutralize natural xenoantibodies in the human recipient. This procedure, hopefully, will permit using xenogeneic short-term grafts as lifesaving devices. At this time experiments will be performed to identify the procedures for obtaining the antigenic preparations active in neutralizing xenoantibodies. The initial studies conducted in animals will deal with in vitro perfusion of heart with xenogeneic serum and selecting the tissue preparations which prevent cytotoxicity of such serum. Thereafter animal experiments will be conducted on survival of an organ xenograft placed into a """"""""neutralized"""""""" recipient.
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