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New roles for cyclin-dependent kinases in T cell biology: linking cell division and differentiation

Nature Reviews Immunology volume 14, pages 261–270 (2014)Cite this article

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Abstract

The proliferation of a few antigen-reactive lymphocytes into a large population of effector cells is a fundamental property of adaptive immunity. The cell division that fuels this process is driven by signals from antigen, co-stimulatory molecules and growth factor receptors, and is controlled by the cyclin-dependent kinase (CDK) cascade. In this Opinion article, we discuss how the CDK cascade provides one potential link between cell division and differentiation through the phosphorylation of immunologically relevant transcription factors, and how components of this pathway might ultimately participate in the decision between tolerance and immunity.

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Figure 1: Regulation of T cell development and differentiation by members of the CDK family.
Figure 2: Models to link cell cycle progression with T cell differentiation.
Figure 3: Regulation of the regulatory T cell programme by CDK2 and p27.

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Acknowledgements

A.D.W. is a member of the Biesecker Pediatric Liver Disease Center at The Children's Hospital of Philadelphia, Pennsylvania, USA. Work relevant to this article by A.D.W. was supported by US National Institutes of Health grants AI054643 and AI070807, and work by P.A.M. was supported by a Goldie Simon Preceptorship Award sponsored by the Lupus Foundation of America Philadelphia Tri-State Chapter, Pennsylvania, USA, and the Pennsylvania Department of Health, USA.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, USA; and The Children's Hospital of Philadelphia Research Institute, Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.,

    Andrew D. Wells & Peter A. Morawski

  2. and The Children's Hospital of Philadelphia Research Institute, Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.,

    Andrew D. Wells & Peter A. Morawski

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  1. Andrew D. Wells
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Corresponding author

Correspondence to Andrew D. Wells.

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The authors declare no competing financial interests.

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Glossary

Anergy

The functional non-responsiveness of antigen-specific T cells.

Autoimmune accelerator locus

(Yaa). A duplication of a 4 Mbp segment of the Y chromosome of inbred BXSB mice containing 19 genes, including Tlr7, that leads to the spontaneous development of systemic autoimmunity similar to systemic lupus erythematosus.

Bioisosteres

In drug design, compounds that have highly similar properties and structures, but varied efficacy, activity or toxicity as a result of minor chemical substitutions.

DN3 to DN4 transition

The transition during thymocyte maturation during which CD4−CD8− double-negative cells undergo T cell receptor-β (TCRβ) rearrangement and downregulate CD25 expression.

G0 phase

(Resting phase). The period of the cell cycle during which the cell is quiescent that lasts until the initiation of cell division.

G1 phase

(Gap1 phase). The phase of the cell cycle during which the cell grows and carries out large amounts of protein synthesis.

Interphase

The period representing the majority of the cell cycle including G1, S and G2 phases, during which the cell increases in size and replicates its DNA.

Interphase CDK

Cyclin-dependent kinases that are active during the interphase (G1, S and G2 phases) of the cell cycle, including CDK2, CDK4 and CDK6.

Nuclear mediator complex

The complex of multiple nuclear proteins that is required to enhance RNA polymerase II-mediated gene transcription.

RNA polymerase II

(RNA Pol II). A 550 kDa, 12-subunit eukaryotic enzyme that is required for the initiation of DNA transcription.

S phase

(Synthesis phase). The phase of the cell cycle during which the genomic DNA is replicated.

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Wells, A., Morawski, P. New roles for cyclin-dependent kinases in T cell biology: linking cell division and differentiation. Nat Rev Immunol 14, 261–270 (2014). https://doi.org/10.1038/nri3625

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