Migratory nonparenchymal cells after organ allotransplantation: with particular reference to chimerism and the liver

Evidence has been summarized that the migration from organ allografts of donor leukocytes of bone marrow origin and their ubiquitous persistence in recipient tissues is the previous unrecognized seminal explanation for allograft acceptance, and the first stage in the development of donor-specific nonreactivity (tolerance). The unusual immunologic privilege of the liver (called hepatic tolerogenicity) has been explained by its heavy content of leukocytes and its diverse lineage profile that includes precursor dendritic cells. In a direct extension of this new and generically applicable paradigm of transplantation immunology, unconditioned patients have been infused with donor bone marrow cells on the day of cadaveric liver, renal, and heart transplantation and treated otherwise with standard FK506-prednisone immunosuppression. All of the first 16 patients on this protocol have good whole organ function 2.5 to 13 months later. Using flow cytometry and qualitative or quantitative PCR techniques to detect donor HLA alleles, and with study of Y chromosomes in female recipients of male organs, persistent multilineage leukocyte chimerism was regularly found in the blood of these recipients. Rejection was diagnosed and successfully treated in 9 (56%) of these first 16 patients and transient GVHD in 2 (12.5%). Sustained donor-specific hyporeactivity as early as 40 days postoperatively was demonstrable with in vitro tests in the majority of these recipients.