The role of heat shock protein (hsp70) in dendritic cell maturation: Hsp70induces the maturation of immature dendritic cells but reduces DC differentiation from monocyte precursors

Members of the heat shock protein (hsp70) family are either constitutively expressed (hsc70) or can be induced by hyperthermic stress (hsp70). Recombi nant hsp70 (rhsp70) stimulates cytokine production from monocytes and enhan ces NK cell proliferation and cytotoxicity. Here we demonstrate that rhsp70 binds to immature dendritic cells (DC) derived from monocyte precursors an d induces their maturation as evidenced by an increase in CD40, CD86 and CD 83 expression. Immature DC stimulated to mature with rhsp70 show an enhance d ability to present tyrosinase peptide to specific CTL. Mature DC did not bind rhsp70, suggesting a down-regulation in the expression of its receptor . When rhsp70 was added to monocyte precursors at the same time as GM-CSF a nd IL-4 it reduced the differentiation of monocytes into DC as shown by a d ecrease in the level of CD40, CD83, CD86 and HLA-DR expression and an incre ase in CD14 expression. The constitutively expressed hsc70 had neither a st imulatory effect on the maturation of immature DC nor did it reduce the dif ferentiation of monocytes into DC. These findings demonstrate the specific ability of rhsp70 to induce the maturation of immature DC. Therefore rhsp70 may be useful for its adjuvant like properties in DC based immunotherapy o f certain tumors.