AUGMENTATION OF DENDRITIC CELLS IN MURINE ORGAN DONORS BY FLT3 LIGANDALTERS THE BALANCE BETWEEN TRANSPLANT TOLERANCE AND IMMUNITY

Treatment of mice with the recently cloned hemopoietic growth factor F lt3 ligand (FL; 10 mu g/day for 10 days) resulted in a large increase in myeloid lineage cells within the liver, While the number of nonpare nchymal cells (NPC) harvested from liver increased about 9-fold, a 90- fold increase was observed in the proportion of CD11c(+) dendritic cel ls (DC) recovered from NPC following overnight (18-h) culture in granu locyte-macrophage CSF, In contrast, only a 50% increase was seen in CD 11c(+) cells within heart single cell suspensions and in the number of DC obtained from hearts after 18-h culture, Liver NPC and heart cell suspensions freshly isolated from 10-day FL-treated animals exhibited increased T cell allostimulatory capacity compared with controls, Over night cultured DC from livers of FL-treated animals expressed both hig her levels of costimulatory molecules (CD80 and CD86) and allostimulat ory activity than those from controls, Heart-derived DC also displayed enhanced stimulatory capacity, Pretreatment of organ donors with FL f or either 5 or 10 days before transplant of organs to normal recipient s abrogated the spontaneous liver allograft acceptance normally observ ed and resulted in delayed or acute graft rejection (median survival t imes, 40 and 12 days, respectively), Heart rejection was significantly accelerated by pretreatment of donors with FL for 5 or 10 days (media n survival times, 8 and 7 days, respectively, vs 12 days in controls), These novel findings reveal the potent immunologic adjuvant propertie s of FL in vivo, They also show that substantial augmentation of the n umber of potential allostimulatory cells in donor organs before transp lantation favors rejection rather than tolerance induction.