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

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.

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