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T cells

mTOR lullabies for naive T cells

Nature Reviews Immunology volume 11, pages 572–573 (2011)Cite this article

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The authors found TSC1 expression in thymocytes and naive T cells. So, they generated mice in which Tsc1 was selectively deleted in T cells to study its immune function. Although Tsc1−/− thymocyte development was normal, the numbers of naive Tsc1−/− T cells in the periphery were significantly reduced. In contrast to adoptively transferred wild-type T cells, Tsc1−/− T cells were undetectable 6 days after their transfer into wild-type mice, indicating a cell-autonomous defect in their survival. However, Tsc1−/− T cells that constitutively expressed the apoptosis inhibitor B cell lymphoma 2 (BCL-2) survived normally, suggesting that naive Tsc1−/− T cells die via the cell-intrinsic apoptotic pathway. Further analysis showed that apoptosis of naive Tsc1−/− T cells was partly dependent on BCL-2-interacting mediator of cell death (BIM) and the generation of reactive oxygen species (ROS). Finally, the numbers of apoptotic naive Tsc1−/− T cells increased in response to T cell receptor (TCR) stimulation. Thus, TSC1 is essential for naive T cell survival.

Naive Tsc1−/− T cells not only had impaired survival, but also lost their quiescence, as they were larger and cycled more rapidly than naive wild-type T cells. In addition, the percentage of Tsc1−/− T cells with the recently activated T cell phenotype CD44+CD122− was increased in both lymphopenic and lymphoreplete environments. Interestingly, Tsc1−/− T cells that constitutively expressed BCL-2 retained this semi-activated T cell phenotype, indicating that the primary effect of TSC1 deficiency is the reversal of T cell quiescence and that the increased T cell apoptosis may be its consequence.

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ORIGINAL RESEARCH PAPER

  1. Yang, K. et al. The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function. Nature Immunol. 17 Jul 2011 (doi:10.1038/ni.2068)

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  1. Maria Papatriantafyllou
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Papatriantafyllou, M. mTOR lullabies for naive T cells. Nat Rev Immunol 11, 572–573 (2011). https://doi.org/10.1038/nri3047

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