Dendritic cell homeostasis is maintained by nonhematopoietic and T-cell-produced Flt3-ligand in steady state and during immune responses.

ABSTRACT

Lymphoid-tissue dendritic cells (DCs) are short-lived and need to be continuously replenished from bone marrow-derived DC progenitor cells. Fms-related tyrosine kinase 3 is expressed during cellular development from hematopoietic progenitors to lymphoid-tissue DCs. Fms-related tyrosine kinase 3 ligand (Flt3L) is an essential, nonredundant cytokine for DC progenitor to lymphoid tissue DC differentiation and maintenance. However, which cells contribute to Flt3L production and how Flt3L cytokine levels are regulated in steady state and during immune reactions remains to be determined. Here we demonstrate that besides nonhematopoietic cells, WT T cells produce Flt3L and contribute to the generation of both classical DCs (cDCs) and plasmacytoid DCs in Flt3L(-/-) mice. Upon stimulation in vitro, CD4(+) T cells produce more Flt3L than CD8(+) T cells. Moreover, in vivo stimulation of naïve OT-II CD4(+) T cells with OVA leads to increase of pre-cDCs and cDCs in draining lymph nodes of Flt3L(-/-) mice in a partially Flt3L-dependent manner. Thus, Flt3L-mediated lymphoid tissue DC homeostasis is regulated by steady-state T cells as well as by proliferative T cells, fostering local development of lymphoid organ resident DCs.