Dendritic cell (DC) development begins in the bone marrow but is not completed until after immature progenitors reach their sites of residence in lymphoid organs. The hematopoietic growth factors regulating these processes are poorly understood. Here we examine the effects of FMS-like tyrosine kinase 3 (Flt3) signaling on macrophage DC progenitors (MDP) in the bone marrow and on peripheral DCs. We find that the MDP compartment is responsive to super–physiologic levels of Flt3 ligand (Flt3L) but is not dependent on Flt3 for its homeostatic maintenance in vivo. In contrast, Flt3 is essential in regulation of homeostatic DC development in the spleen where it is required to maintain normal numbers of DCs by controlling their division in the periphery.

The zinc finger transcription factor zDC is uniquely expressed by the cDC lineage among immune cells, and the insertion of diphtheria toxin receptor cDNA into the zDC locus allows specific ablation of the cDC lineage in mice.

Despite a growing interest in CD4 ϩ CD25 ϩ regulatory T cells (T reg ) that play a major role in self-tolerance and immunoregulation, fundamental parameters of the biology and homeostasis of these cells are poorly known. Here, we show that this population is composed of two T reg subsets that have distinct phenotypes and homeostasis in normal unmanipulated mice. In the steady state, some T reg remain quiescent and have a long lifespan, in the order of months, whereas the other T reg are dividing extensively and express multiple activation markers. After adoptive transfer, tissue-specific T reg rapidly divide and expand preferentially in lymph nodes draining their target self-antigens. These results reveal the existence of a cycling T reg subset composed of autoreactive T reg that are continuously activated by tissue self-antigens.