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

Nature Immunology volume 5, pages 31–37 (2004)Cite this article

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.

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Figure 1: Cell cycle characteristics of naive and memory transgenic cells.
Figure 2: Expression of INK4 inhibitors in naive and memory transgenic cells.
Figure 3: Cip-Kip molecules, cyclin D and cyclin E complexes in naive (N) and sorted G0/G1 memory transgenic cells (M).
Figure 4: Comparison of cell cycle parameters in naive and memory CD8 T cells from normal mice.
Figure 5: Effect of anti-cyclin D3 on the cell cycle entry and progression of polyclonal memory T cells.

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Acknowledgements

We thank C. Garcia for cell sorting; J. Lipecka for confocal microscopy; M. Serrano, T. Toda, F. Uhlmann, C. Reis e Sousa, V. Dulic, V. Boussiotis, F. Sigaux, A.A. Freitas, A. Sarukhan, A. Peixoto, S. Guillaume and C. Saint-Ruf for discussions; and P. Sicinski for allowing us to cite his unpublished data. Supported by Association pour la Recherche sur le Cancer and Ligue pour la Recherche sur le Cancer, and the Technology and Science Foundation (Portugal) and Fondation Recherche Médicale (both H.V.-F.).

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  1. Institut National de la Santé et de la Recherche Médicale U591, Institut Necker, 156 Rue de Vaugirard, Paris, 75015, France

    Henrique Veiga-Fernandes & Benedita Rocha

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  1. Henrique Veiga-Fernandes
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Correspondence to Henrique Veiga-Fernandes.

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Veiga-Fernandes, H., Rocha, B. High expression of active CDK6 in the cytoplasm of CD8 memory cells favors rapid division. Nat Immunol 5, 31–37 (2004). https://doi.org/10.1038/ni1015

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