EFFECTS OF CHIMERIC CELLS FOLLOWING DONOR BONE-MARROW INFUSIONS AS DETECTED BY PCR-FLOW ASSAYS IN KIDNEY-TRANSPLANT RECIPIENTS

40 recipients of first cadaver kidney transplants were given periopera tive donor vertebral bone marrow infusions (DBMC), compared with 100 c ontrols who did not receive donor bone marrow, The immunosuppressive r egimen included OKT3, Tacrolimus, and steroid maintenance therapy, and , in some patients, newly introduced mycophenolate mofetil. This repor t describes the 24-mo actuarial follow-up and several immunological mo nitoring studies including sequential measurements of donor bone marro w lineage subset chimerism by the recently reported PCR-flow assay, Th is is a sensitive in situ PCR detection system for donor versus recipi ent histocompatibility genes as well as cell surface CD epitope marker s using flow cytometry. The results indicate (a) the stabilization of the donor CD3+ and CD34+ cells in recipient peripheral blood at levels below 1% between 6 mo and 1 yr postoperatively, with a 10-fold higher level of donor cell chimerism of these lineages in recipient iliac cr est marrow; (b) significantly lower levels of chimerism in peripheral blood up to 6 mo postoperatively in patients who had early acute (reve rsible) rejection episodes compared with those who did not; (c) a high er degree of chimerism seen in patients who were class II MHC HLA DR i dentical with their donors; (c) the identification of a high proportio n of the donor bone marrow derived CD3 dimly staining subset of T cell s (to which regulatory functions have been ascribed) in recipient peri pheral blood and especially in recipient bone marrow; and (e) an unexp ectedly increased susceptibility to clinically significant infections (primarily viral), and even death in the DBMC-infused group, compared with controls, but no graft losses because of rejection in the DBMC-in fused group, Mixed lymphocyte culture assays showed a trend toward a g reater number of nonspecifically low reactors in the DBMC group, as we ll as a greater number of nonspecifically high reactors in the control s (P = 0.058), The autologous mixed lymphocyte reaction also indicated a trend towards nonspecific immune activation in the DBMC group. Fina lly, anti-cytomegaloviral IgG antibody reactivity was significantly in hibited in the DBMC group 4-6 mo postoperatively (P = < 0.05), In the controls, there were no donor cell lineages detected by PCR-flow in th e peripheral blood, These rather unexpected findings, indicating a mor e depressed cellular and humoral immune capacity in the DBMC cadaver k idney transplant recipients in this relatively early follow-up period, are discussed relevant to chimerism, MHC restriction, and suppressor activity brought about by specialized DBMC subsets, which still need t o be defined.