High expression of active CDK6 in the cytoplasm of CD8 memory cells favors rapid division

Abstract

Antigen-driven CD8 memory T cell proliferation is more rapid than that of naive T cells, ensuring efficient control of the pathogen after reinfection. We show here that naive and memory cells are in different states of G0/G1 arrest. Naive cells are in a classical state of G0/G1 arrest, with high expression of p27Kip1 and low CDK6 and CDK2 kinase activity. In contrast, memory cells have low expression of p27Kip1 and high CDK6 kinase activity. This preactivated kinase is associated with cyclin D3 in the cytoplasm, and neutralization of these complexes with antibody to cyclin D3 blocks the rapid division of memory cells. Therefore G0/G1 memory cells are at a unique preactivated state that favors rapid division after antigen stimulation.