The purpose of this report was to determine the effect of prion protein (PrP) gene disruption on T lymphocyte function. Previous studies have suggested that normal cellular prion protein (PrPc) binds to copper and Cu2+ is essential for interleukin-2 (IL-2) mRNA synthesis. In this study, IL-2 mRNA levels in a copper-deficient condition were investigated using T lymphocytes from prion protein gene-deficient (PrP0/0) and wild-type mice. Results showed that Cu2+ deficiency had no effect on PrPc expression in Con A-activated splenocytes. However, a delay in IL-2 gene expression was observed in PrP0/0 mouse T lymphocyte cultures using Con A and Cu2+-chelator. These results suggest that PrPc expression may play an important role in rapid Cu2+ transfer in T lymphocytes. The rapid transfer of Cu2+ in murine T lymphocytes could be one of the normal functions of PrPc. (C) 2003 Elsevier Inc. All rights reserved.