Rj. Steptoe et al., AUGMENTATION OF DENDRITIC CELLS IN MURINE ORGAN DONORS BY FLT3 LIGANDALTERS THE BALANCE BETWEEN TRANSPLANT TOLERANCE AND IMMUNITY, The Journal of immunology, 159(11), 1997, pp. 5483-5491
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.