T-cell education of dendritic cell responsiveness

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIAID	IMMUNO-1

Authors

• Kaveh Abdi
• Nevil Singh
• Polly Matzinger

Abstract

LPS-activated Dendritic Cells (DCs) are thought to follow a set program: first secreting inflammatory cytokines (such as IL-12p75) and then becoming refractory to further stimulation (i.e. “exhausted”). Here we show that these concepts need to be reconsidered. First, LPS-activated mouse DCs produce copious amounts of IL-12p40, but no IL-12p75 unless they receive additional signals from T cells (i.e. IFN-gamma, CD40-ligand plus a combination of GM-CSF and IL-4). Although LPS-stimulated DCs do lose their responsiveness to LPS about 24 hours after stimulation, they nevertheless remain perfectly capable of making inflammatory cytokines in response to signals from activated T cells, and to a combination of CD40-ligand plus soluble T-cell derived signals. In addition, far from being rigidly programmed by the original activating stimulus, the DCs retain sufficient plasticity to respond differentially to interactions with TH0, TH1, TH2 and TH17 T cells, showing that T cells are not merely amplifiers of DC-differentiation programs originally set by the DC-activating stimulus, but can change the subsequent activity of the DCs with which they interact. These data indicate that DCs are not programmed to respond to stimulation with a pre-determined series of events, but remain sensitive to their environment and can change their differentiation accordingly.

back to top