The normal cellular form of prion protein modulates T cell responses

Expression of the normal form of prion protein (PrP C) has been reported on a wide range cells including lymphocytes and antigen presenting cells, however the functional role of PrP C remains to be fully elucidated. Here we report the effect of reintroducing the PrP gene into splenocytes derived from prion knockout (PrP 0/0) mice and comparing their responses with splenocytes lacking a functional PrP gene. Reintroduction of the PrP gene was carried out by transfecting cells with pC1PrPEH, a plasmid expressing mouse PrP. Following transfection, T cells demonstrated an increased capacity to proliferate in response to ConA and PMA/ionomycin compared to T cells lacking the functional PrP gene. A bioassay used to determine IL-2 levels indicated that the reintroduction of the PrP gene might enhance IL-2 expression in response to ConA. Levels of IFN-γ produced also showed an increase following transfection with PrP expressing plasmid. A comparison between splenocytes derived from PrP 0/0 and PrP +/+ also demonstrated some differences in cytokine production and proliferation. Together these results show PrP C has an impact on the normal T cell activation and proliferation in response to mitogens and also potentially antigen responsiveness.