Hedrick, S.M., Ch'en, I.L. & Alves, B.N. Intertwined pathways of programmed cell death in immunity. Immunol. Rev. 236, 41–53 (2010).
Surh, C.D. & Sprent, J. Homeostasis of naive and memory T cells. Immunity 29, 848–862 (2008).
Takada, K. & Jameson, S.C. Naive T cell homeostasis: from awareness of space to a sense of place. Nat. Rev. Immunol. 9, 823–832 (2009).
Glynne, R., Ghandour, G., Rayner, J., Mack, D.H. & Goodnow, C.C. B-lymphocyte quiescence, tolerance and activation as viewed by global gene expression profiling on microarrays. Immunol. Rev. 176, 216–246 (2000).
Teague, T.K. et al. Activation changes the spectrum but not the diversity of genes expressed by T cells. Proc. Natl. Acad. Sci. USA 96, 12691–12696 (1999).
Berger, M. et al. An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence. Nat. Immunol. 11, 335–343 (2010).
Modiano, J.F., Johnson, L.D. & Bellgrau, D. Negative regulators in homeostasis of naive peripheral T cells. Immunol. Res. 41, 137–153 (2008).
Yusuf, I. & Fruman, D.A. Regulation of quiescence in lymphocytes. Trends Immunol. 24, 380–386 (2003).
Kuo, C.T., Veselits, M.L. & Leiden, J.M. LKLF: A transcriptional regulator of single-positive T cell quiescence and survival. Science 277, 1986–1990 (1997).
Kerdiles, Y.M. et al. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nat. Immunol. 10, 176–184 (2009).
Kerdiles, Y.M. et al. Foxo transcription factors control regulatory T cell development and function. Immunity 33, 890–904 (2010).
Ouyang, W., Beckett, O., Flavell, R.A. & Li, M.O. An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance. Immunity 30, 358–371 (2009).
Ouyang, W. et al. Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells. Nat. Immunol. 11, 618–627 (2010).
Carlson, C.M. et al. Kruppel-like factor 2 regulates thymocyte and T-cell migration. Nature 442, 299–302 (2006).
Takada, K. et al. Kruppel-like factor 2 is required for trafficking but not quiescence in postactivated T cells. J. Immunol. 186, 775–783 (2011).
Jones, R.G. & Thompson, C.B. Revving the engine: signal transduction fuels T cell activation. Immunity 27, 173–178 (2007).
Pearce, E.L. Metabolism in T cell activation and differentiation. Curr. Opin. Immunol. 22, 314–320 (2010).
Zoncu, R., Efeyan, A. & Sabatini, D.M. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 12, 21–35 (2011).
Weichhart, T. & Saemann, M.D. The multiple facets of mTOR in immunity. Trends Immunol. 30, 218–226 (2009).
Powell, J.D. & Delgoffe, G.M. The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity 33, 301–311 (2010).
Finlay, D. & Cantrell, D.A. Metabolism, migration and memory in cytotoxic T cells. Nat. Rev. Immunol. 11, 109–117 (2011).
Kwiatkowski, D.J. et al. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum. Mol. Genet. 11, 525–534 (2002).
Tait, S.W. & Green, D.R. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat. Rev. Mol. Cell Biol. 11, 621–632 (2010).
Pendergrass, W., Wolf, N. & Poot, M. Efficacy of MitoTracker Green and CMXrosamine to measure changes in mitochondrial membrane potentials in living cells and tissues. Cytometry A 61, 162–169 (2004).
Sinclair, L.V. et al. Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking. Nat. Immunol. 9, 513–521 (2008).
Liu, G., Yang, K., Burns, S., Shrestha, S. & Chi, H. The S1P1-mTOR axis directs the reciprocal differentiation of TH1 and Treg cells. Nat. Immunol. 11, 1047–1056 (2010).
Hildeman, D.A. et al. Reactive oxygen species regulate activation-induced T cell apoptosis. Immunity 10, 735–744 (1999).
Menon, S. et al. COP9 signalosome subunit 8 is essential for peripheral T cell homeostasis and antigen receptor-induced entry into the cell cycle from quiescence. Nat. Immunol. 8, 1236–1245 (2007).
Boyman, O., Cho, J.H., Tan, J.T., Surh, C.D. & Sprent, J. A major histocompatibility complex class I-dependent subset of memory phenotype CD8+ cells. J. Exp. Med. 203, 1817–1825 (2006).
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545–15550 (2005).
Lee, K. et al. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 32, 743–753 (2010).
Delgoffe, G.M. et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 12, 295–303 (2011).
Jones, R.G. et al. Protein kinase B regulates T lymphocyte survival, nuclear factor kappaB activation, and Bcl-XL levels in vivo. J. Exp. Med. 191, 1721–1734 (2000).
Inoki, K., Zhu, T. & Guan, K.L. TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577–590 (2003).
Manning, B.D., Tee, A.R., Logsdon, M.N., Blenis, J. & Cantley, L.C. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 10, 151–162 (2002).
Weichhart, T. et al. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29, 565–577 (2008).
Gan, B. et al. mTORC1-dependent and -independent regulation of stem cell renewal, differentiation, and mobilization. Proc. Natl. Acad. Sci. USA 105, 19384–19389 (2008).
Chen, C. et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J. Exp. Med. 205, 2397–2408 (2008).
Choo, A.Y. et al. Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply. Mol. Cell 38, 487–499 (2010).
Ghosh, S. et al. Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-κB activation and cell survival. Cancer Cell 10, 215–226 (2006).
Rathmell, J.C., Farkash, E.A., Gao, W. & Thompson, C.B. IL-7 enhances the survival and maintains the size of naive T cells. J. Immunol. 167, 6869–6876 (2001).
Araki, K. et al. mTOR regulates memory CD8 T-cell differentiation. Nature 460, 108–112 (2009).
Pearce, E.L. et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460, 103–107 (2009).
Rao, R.R., Li, Q., Odunsi, K. & Shrikant, P.A. The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity 32, 67–78 (2010).
Delgoffe, G.M. et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 30, 832–844 (2009).
Liu, G. et al. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat. Immunol. 10, 769–777 (2009).
Houtkooper, R.H., Williams, R.W. & Auwerx, J. Metabolic networks of longevity. Cell 142, 9–14 (2010).
Shiota, C., Woo, J.T., Lindner, J., Shelton, K.D. & Magnuson, M.A. Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is essential for fetal growth and viability. Dev. Cell 11, 583–589 (2006).
Huang, d.W., Sherman, B.T. & Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57 (2009).