Differential constitutive and activation-dependent expression of prion protein in human peripheral blood leucocytes

The cellular isoform of the prion protein (PrPC) is a cell surface glycopro tein that has recently been shown to play a role in haemopoietic cell activ ation and proliferation. We have characterized the constitutive expression of PrPC on human peripheral blood (pB) cell populations, using PrP-specific antibodies in a multiparameter flow cytometry approach. We found that T ce lls, NK cells and monocytes exhibit similar PrPC levels, whereas PrPC surfa ce staining on B cells was significantly lower and was virtually absent on granulocytes. Within the T-cell compartment, CD8+ cells showed a significan tly higher PrPC expression than CD4+ cells. Similarly, CD3+ cells co-expres sing the activation marker CD56 (N-CAM) exhibited significantly higher PrPC expression levels than their CD56- counterparts. Culture of CD14+ pB monoc ytes for 12-48 h in the presence of interferon gamma (IFN-gamma) resulted i n a significant increase in PrPC expression in a time- and concentration-de pendent manner. This effect was partially abrogated by the addition of the metabolic inhibitor cycloheximide, indicating the role of protein synthesis in this process. Our results show that PrPC expression on human haemopoiet ic cells correlates with the activation and developmental status of these c ells, suggesting an important functional role of PrPC in the haemopoietic s ystem.