Cell cycle-related acquisition of cytotoxic mediators defines the progressive differentiation to effector status for virus-specific CD8 T cells

Abstract

Although analysis of virus-specific CTL function at the peak of infection suggests that granzyme (grz) and perforin (pfp) gene expression is not coregulated, early differentiation events leading to acquisition of function are poorly understood. Using a combination of CFSE dilutions and single-cell RT-PCR, effector gene expression was determined early after CTL activation. There were low levels of pfp and grz expression at division 3, with increased expression by divisions 6-8. The increase in effector mRNA expression with division correlated with increasing ex vivo cytotoxicity. Of the mRNA transcripts detected at division 3, there was an increased frequency of grzB and grzK (compared with g..