Hematolymphoid cell trafficking, microchimerism, and GVH reactions after liver, bone marrow, and heart transplantation.

Abstract

T HE RECENT discovery of ubiquitously located small numbers of donor leukocytes (microchimerism) in human kidneys, livers, and other organs 1 --{) up to 29 years posttransplantation has raised questions about the migra tion of the chimeric cells and their role in the induction and perpetuation of graft acceptance. In the human studies, the most prominent of the peripheralized donor leukocytes appeared morphologically to be the dendritic cells delin­ eated as a special white cell lineage in 1973 by Steinman and Cohn7- 10 and normally associated with organ immu­ nogenicity rather than tolerogenicity.II-12 We report here an investigation of the cell migration in unmodified versus immunosuppressed Brown Norway (BN) rat recipients of Lewis (LEW) livers with emphasis on the kinetics, loca­ tion, and the reaction elicited by these cells in the recipient lymphoid organs. We also looked for histopathologic signs in these ani­ mals of the graft versus host (OVH) reaction that we have postulated to be an integral part of organ graft accep­ tance.1,5,6 To magnify the OVH effect, we developed a model in which the lethal OVHD potential of the liver passenger leukocytes could be routinely demonstrated in the LEW to BN strain combination.