High expression of active CDK6 in the cytoplasm of CD8 memory cells favors rapid division.
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.
Veiga-Fernandes
Henrique
H
Institut National de la Santé et de la Recherche Médicale U591, Institut Necker, 156 Rue de Vaugirard, 75015 Paris, France. veiga@necker.fr
Rocha
Benedita
B
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D018797:Cell Cycle Proteins / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D056743:Cyclin D3; D051361:Cyclin-Dependent Kinase 6; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000276:immunology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000276:immunology; D016213:Cyclins / Q000037:antagonists & inhibitors / Q000276:immunology; D003593:Cytoplasm / Q000201:enzymology; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008858:Microscopy, Phase-Contrast; D025521:Tumor Suppressor Proteins / Q000276:immunology
C534697:Ccnd3 protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D056743:Cyclin D3; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495912:Cdk6 protein, mouse; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases