Antigenic Restimulation of Virus-Specific Memory CD8 + T Cells Requires Days of Lytic Protein Accumulation for Maximal Cytotoxic Capacity

Abstract

Antigen-specific CD8 + T cells play a major role in controlling most virus infections, primarily by perforin (PRF)- and granzyme B (GrB)-mediated apoptosis. There is considerable controversy regarding whether PRF is constitutively expressed, rapidly increased similarly to a cytokine, or delayed in its expression with more prolonged stimulation in virus-specific memory CD8 + T cells. In this study, the degree of cytotoxic capacity of virus-specific memory CD8 + T cells was directly proportional to the content of lytic molecules, which required antigenic stimulation over several days for maximal levels. This appeared to be modulated by increases in GrB transcription and microRNA-mediated posttranscriptional regulation of PRF expression. Clarifying the requirements for maximal cytotoxic capacity is critical to understanding how viral clearance might be mediated by memory cells and what functions should be induced by vaccines and immunotherapies.