Treatment of neonatal mice with Flt3 ligand leads to changes in dendritic cell subpopulations associated with enhanced IL‐12 and IFN‐α production

Abstract

Treatment with the hematopoietic growth factor Flt3 ligand (FL) increases DC numbers in neonatal mice and enhances their resistance against intracellular pathogens. Flow cytometric analysis showed the presence of conventional DC (cDC) and plasmacytoid pre-DC (pDC) in neonatal spleens from untreated and FL-treated mice. CD8 § and MHC class II expression on cDC and pDC was higher on DC from FL-treated mice than on DC from control littermates. After FL treatment, two additional subpopulations of DC-lineage cells were found that were able to produce IL-12 and IFN- § . The IL-12 production of cDC from FLtreated animals was more than 50-fold increased and their ability to stimulate T cell proliferation was also increased. We conclude that the enhanced resistance against intracellular pathogens was due to increased numbers of DC-lineage cells and their increased ability to produce the essential cytokines.

Enhancement of Dendritic Cell Production by Fms-Like Tyrosine Kinase-3 Ligand Increases the Resistance of Mice to a Burn Wound Infection

“…The specific mechanism by which Flt3L enhances dendritic cell functions in this model is not known. However, other studies have reported that Flt3L-generated dendritic cells express higher levels of MHC class II, CD86, and CD40, produce higher levels of IL-12, and are more efficient at stimulating T cell proliferation than normal dendritic cells from mice that did not receive Flt3L treatments (38,39). Future studies will be performed to fully characterize and compare dendritic cells isolated from normal and Flt3L-treated mice.…”

Neonatal Innate Immunity to Infectious Agents

“…In particular, FL induced increases in DC numbers as well as IL-12 production by these cells (96). The increased IL-12 production may be crucial in defense against Listeria in vivo through stimulating IFN-␥ release by T cells and NK cells and most likely explains the increased survival of FL-treated neonatal mice.…”

“…The overall efficiency of CD8-dependent T-cell function in fetal or neonatal life, however, remains unclear. Evidence suggests that neonatal CD4 ϩ T cells are deficient in activationassociated intracellular signaling and require high levels of costimulation to achieve maximal activation (2,27,96). In this regard it is noteworthy that CD4 ϩ T cells play an essential role in promoting the long-term activation and terminal differentiation of CD8 ϩ T cells and in reactivation of CD8 ϩ memory cells.…”

Development of Murine Plasmacytoid Dendritic Cells Defined by Increased Expression of an Inhibitory NK Receptor, Ly49Q

“…There have been reports that cord blood PDCs show reduced IFN-␣ production with CpG (28) and that newly developed CD11c high CD45RA ϩ B220 ϩ splenic PDCs (using Flt3 ligand and newborn mice), most of which are negative for CD4, are less able to produce IFN-␣ and IL-12 in response to HSV-1 than PDCs from normal adult mice (29). Ly49Q Ϫ marrow PDCs are possibly related in differentiation stage with the newly developed CD11c high CD45RA ϩ B220 ϩ splenic PDCs induced by Flt3 ligand, because PDCs in marrow also expressed high levels of CD11c relative to spleen PDCs.…”