The overall aim of this project is characterization of the presence, distribution, and function of donor derived hematopoietic cells in recipients of first cadaveric kidney transplants that are accompanied by the simultaneous administration of donor bone marrow cells. The approach will utilize a new and sensitive analytic tool developed in the laboratory, the PCR-Flow assay, that identifies the genotype and selected cell surface markers on individual cells. Preliminary evidence in 45 patients 3 to 26 months after transplantation, compared with 120 controls transplanted without donor bone marrow, shows that marrow infused patients have both a state of microchimerism and a non-specific state of immunosuppression. The proposal is to enlarge the study to 125 marrow treated patients and 250 controls, in order to relate the presence of donor cells of particular phenotype and function to clinical status, and to determine which patients may have immunosuppression discontinued. Studies will continue on the cells freshly obtained from cadaveric donors, comparing MLC and CML responsiveness and regulatory capability of subsets of bone marrow, spleen and lymph node. After transplantation, peripheral blood cells, bone marrow, and peripheral lymph nodes of recipients will be sampled at intervals for functional and phenotypic study of subsets, including expression of cytokine mRNA and protein. Results will be correlated with levels and character of chimerism found with several clinical parameters, including the presence of antibodies to HLA and transplant biopsies.
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