Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity

Abstract

The model that dendritic cell (DC) "maturation" describes the change from an immature, antigen-capturing cell to a mature, antigen-presenting cell is well-established. Classification of DCs in terms of function has been problematic previously. It is therefore proposed that mature and not immature DCs are responsible for antigen presentation and stimulation of T cells. Furthermore, DC antigen presentation to T cells can have two outcomes: tolerance or immunity. The particular outcomes appear to be determined by the activation state of the mature DC. DCs can be activated by a range of environmental stimuli or "danger signals". Here, the hypothesis is advanced that activated, mature DCs induce T cell immunity, and resting, nonactivated but fully differentiated mature antigen-presenting DCs can induce tolerance. This proposal extends to conventional DCs and plasmacytoid DCs. The paper also concentrates on the spleen as a site for DC maturation, in light of evidence from this laboratory for differentiation of DCs from splenic precursors in long-term, stroma-dependent cultures. The hypothesis advanced here serves to simplify many current issues regarding DC maturation and function.