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T cell responses

mTOR mixes up a recipe for success

Nature Reviews Immunology volume 10, pages 86–87 (2010)Cite this article

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The transcription factor T-bet (also known as TBX21) is a master regulator of differentiation of type 1 CD8+ effector T cells — which produce interferon-γ (IFNγ) — and its expression can be induced by interleukin-12 (IL-12). Although a previous study has indicated that mTOR has a role in the differentiation of effector versus memory CD8+ T cells (see Further reading), until now it has been unclear how cell surface signals from antigen, co-stimulatory and cytokine receptors are integrated in a transcriptional response and how mTOR functions in this pathway.

In this study, Rao and colleagues used naive OT-I T cell receptor (TCR)-transgenic CD8+ T cells stimulated with an adherent cell line expressing antigen specific for the OT-I TCR and the co-stimulatory molecule CD80 (BOK cells). The addition of IL-12 to the cell cultures resulted in robust IFNγ production by the OT-I cells. This type 1 effector commitment depended on increased and, in particular, prolonged phosphorylation (activation) of mTOR and its downstream targets in the OT-I cells. Increased mTOR activity in the presence of IL-12 resulted from increased activity of the phosphoinositide 3-kinase (PI3K)–AKT pathway, which signals downstream of the receptors for all three types of instructive signal. Maintenance of mTOR activation by IL-12 also required signal transducer and activator of transcription 4 (STAT4).

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References

ORIGINAL RESEARCH PAPER

  1. Rao, R. R. et al. The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and eomesodermin. Immunity 7 Jan 2010 (doi:10.1016/j.immuni.2009.10.010)

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FURTHER READING

  1. Minton, K. T cell responses: Quantity and quality control by mTOR. Nature Rev. Immunol. 9, 534 (2009)

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Authors
  1. Kirsty Minton
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Minton, K. mTOR mixes up a recipe for success. Nat Rev Immunol 10, 86–87 (2010). https://doi.org/10.1038/nri2716

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  • DOI: https://doi.org/10.1038/nri2716

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