Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells

PLoS ONE

Volumn 9, Issue 8, 2014, Pages

  Cao, Yilin ^a   Rathmell, Jeffrey C ^a   Macintyre, Andrew N ^a  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD28 ANTIGEN; CD3 ANTIGEN; GLUTAMINE; HEXOKINASE; HEXOKINASE 1; HEXOKINASE 2; HEXOKINASE 3; INTERLEUKIN 15; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 2 RECEPTOR BETA; INTERLEUKIN 2 RECEPTOR GAMMA; INTERLEUKIN 7; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PYRUVATE KINASE; PYRUVATE KINASE M2 ISOFORM; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG; GLUCOSE;

ADAPTIVE IMMUNITY; AEROBIC METABOLISM; AMINO ACID METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL GROWTH; CELL MEDIATED CYTOTOXICITY; CELL SURVIVAL; CONTROLLED STUDY; CYTOKINE RELEASE; ENZYME ACTIVATION; EX VIVO STUDY; FEMALE; GLUCOSE METABOLISM; GLYCOLYSIS; INTRACELLULAR SIGNALING; LYMPHOCYTE PROLIFERATION; MALE; METABOLIC INHIBITION; METABOLIC REGULATION; METABOLIC REPROGRAMMING; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; MITOCHONDRIAL VOLUME; MOUSE; NONHUMAN; PROTEIN EXPRESSION; T LYMPHOCYTE ACTIVATION; ANIMAL; CELL LINEAGE; CYTOTOXIC T LYMPHOCYTE; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; METABOLISM; MITOCHONDRION;

ADAPTIVE IMMUNITY; AEROBIOSIS; ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CELL LINEAGE; GLUCOSE; GLYCOLYSIS; LYMPHOCYTE ACTIVATION; METABOLIC NETWORKS AND PATHWAYS; MICE; MITOCHONDRIA; T-LYMPHOCYTES, CYTOTOXIC;

EID: 84905510173     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0104104     Document Type: Article

References (48)

1. MacIver NJ, Michalek RD, Rathmell JC (2013) Metabolic regulation of T lymphocytes. Annu Rev Immunol 31: 259-283.
2. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, et al. (2011) Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 186: 3299-3303.
3. Wang R, Dillon C, Shi L, Milasta S, Carter R, et al. (2011) The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 35: 871-882.
4. Shi LZ, Wang R, Huang G, Vogel P, Neale G, et al. (2011) HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208: 1367-1376.
5. He S, Kato K, Jiang J, Wahl DR, Mineishi S, et al. (2011) Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells. PLoS One 6: e20107.
6. Gubser PM, Bantug GR, Razik L, Fischer M, Dimeloe S, et al. (2013) Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch. Nat Immunol 14: 1064-1072.
7. van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC, et al. (2012) Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36: 68-78.
8. Sinclair LV, Rolf J, Emslie E, Shi YB, Taylor PM, et al. (2013) Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat Immunol 14: 500-508.
9. Frauwirth K, Riley J, Harris M, Parry R, Rathmell J, et al. (2002) The CD28 signaling pathway regulates glucose metabolism. Immunity 16: 769-777. (Pubitemid 34786476)
10. Jacobs SR, Herman CE, Maciver NJ, Wofford JA, Wieman HL, et al. (2008) Glucose uptake is limiting in T cell activation and requires CD28-mediated Aktdependent and independent pathways. J Immunol 180: 4476-4486.
11. Chakrabarti R, Jung CY, Lee TP, Liu H, Mookerjee BK (1994) Changes in glucose transport and transporter isoforms during the activation of human peripheral blood lymphocytes by phytohemagglutinin. J Immunol 152: 2660-2668. (Pubitemid 24097960)
12. Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, et al. (2014) The Glucose Transporter Glut1 Is Selectively Essential for CD4 T Cell Activation and Effector Function. Cell Metab In press.
13. Marjanovic S, Wielburski A, Nelson BD (1988) Effect of phorbol myristate acetate and concanavalin A on the glycolytic enzymes of human peripheral lymphocytes. Biochim Biophys Acta 970: 1-6.
14. Marjanovic S, Eriksson I, Nelson BD (1990) Expression of a new set of glycolytic isozymes in activated human peripheral lymphocytes. Biochim Biophys Acta 1087: 1-6. (Pubitemid 20298390)
15. O'Rourke AM, Rider CC (1989) Glucose, glutamine and ketone body utilisation by resting and concanavalin A activated rat splenic lymphocytes. Biochim Biophys Acta 1010: 342-345. (Pubitemid 19058632)
16. Macintyre AN, Rathmell JC (2013) Activated lymphocytes as a metabolic model for carcinogenesis. Cancer & Metabolism 1: 5.
17. Lunt S, Vander Heiden M (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27: 441-464.
18. Chen L, Flies DB (2013) Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol 13: 227-242.
19. Wang X, Rickert M, Garcia KC (2005) Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors. Science 310: 1159-1163. (Pubitemid 41681737)
20. Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA (2006) Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci U S A 103: 2788-2793.
21. Robb RJ, Rusk CM, Yodoi J, Greene WC (1987) Interleukin 2 binding molecule distinct from the Tac protein: analysis of its role in formation of high-affinity receptors. Proc Natl Acad Sci U S A 84: 2002-2006. (Pubitemid 17054137)
22. Rathmell J, Vander Heiden M, Harris M, Frauwirth K, Thompson C (2000) In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Mol Cell 6: 683-692.
23. Keast D, Newsholme EA (1991) Effect of B- and T-cell mitogens on the maximum activities of hexokinase, lactate dehydrogenase, citrate synthase and glutaminase in bone marrow cells and thymocytes of the rat during four hours of culture. Int J Biochem 23: 823-826.
24. Tamada M, Suematsu M, Saya H (2012) Pyruvate kinase M2: multiple faces for conferring benefits on cancer cells. Clin Cancer Res 18: 5554-5561.
25. Xu X, Ye L, Araki K, Ahmed R (2012) mTOR, linking metabolism and immunity. Semin Immunol 24: 429-435.
26. Zhao Y, Wieman HL, Jacobs SR, Rathmell JC (2008) Mechanisms and methods in glucose metabolism and cell death. Methods Enzymol 442: 439-457.
27. Rochman Y, Spolski R, Leonard WJ (2009) New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol 9: 480-490.
28. Lee HW, Park SJ, Choi BK, Kim HH, Nam KO, et al. (2002) 4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1. J Immunol 169: 4882-4888. (Pubitemid 35217152)
29. Shuford WW, Klussman K, Tritchler DD, Loo DT, Chalupny J, et al. (1997) 4-1BB costimulatory signals preferentially induce CD8 + T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J Exp Med 186: 47-55. (Pubitemid 27304846)
30. Croft M, So T, Duan W, Soroosh P (2009) The significance of OX40 and OX40L to T-cell biology and immune disease. Immunol Rev 229: 173-191.
31. Roederer M (2011) Interpretation of cellular proliferation data: Avoid the panglossian. Cytometry Part A 79A: 95-101.
32. Chang CH, Curtis JD, Maggi LB, Jr., Faubert B, Villarino AV, et al. (2013) Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153: 1239-1251.
33. van der Windt GJ, O'Sullivan D, Everts B, Huang SC, Buck MD, et al. (2013) CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability. Proc Natl Acad Sci U S A 110: 14336-14341.
34. Cham CM, Gajewski TF (2005) Glucose availability regulates IFN-gamma production and p70S6 kinase activation in CD8+ effector T cells. J Immunol 174: 4670-4677.
35. van der Windt G, Everts B, Chang C, Curtis J, Freitas T, et al. (2012) Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36: 68-78.
36. Nakaya M, Xiao Y, Zhou X, Chang JH, Chang M, et al. (2014) Inflammatory T Cell Responses Rely on Amino Acid Transporter ASCT2 Facilitation of Glutamine Uptake and mTORC1 Kinase Activation. Immunity 40: 692-705.
37. Michalek RD, Gerriets VA, Nichols AG, Inoue M, Kazmin D, et al. (2011) Estrogen-related receptor-alpha is a metabolic regulator of effector T-cell activation and differentiation. Proc Natl Acad Sci U S A 108: 18348-18353.
38. Gatza E, Wahl DR, Opipari AW, Sundberg TB, Reddy P, et al. (2011) Manipulating the bioenergetics of alloreactive T cells causes their selective apoptosis and arrests graft-versus-host disease. Sci Transl Med 3: 67ra68.
39. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, et al. (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452: 230-233. (Pubitemid 351380249)
40. Wong N, De Melo J, Tang D (2013) PKM2, a Central Point of Regulation in Cancer Metabolism. Int J Cell Biol 2013: 242513.
41. Foulds KE, Zenewicz LA, Shedlock DJ, Jiang J, Troy AE, et al. (2002) Cutting edge: CD4 and CD8 T cells are intrinsically different in their proliferative responses. J Immunol 168: 1528-1532. (Pubitemid 34135743)
42. Whitmire JK, Ahmed R (2000) Costimulation in antiviral immunity: differential requirements for CD4(+) and CD8(+) T cell responses. Curr Opin Immunol 12: 448-455. (Pubitemid 30410352)
43. De Boer RJ, Homann D, Perelson AS (2003) Different dynamics of CD4+ and CD8+ T cell responses during and after acute lymphocytic choriomeningitis virus infection. J Immunol 171: 3928-3935. (Pubitemid 37238664)
44. Campbell SB, Komata T, Kelso A (2000) Differential effects of CD4 and CD8 engagement on the development of cytokine profiles of murine CD4+ and CD8+ T lymphocytes. Immunology 99: 394-401. (Pubitemid 30137704)
45. Ostroukhova M, Goplen N, Karim MZ, Michalec L, Guo L, et al. (2012) The role of low-level lactate production in airway inflammation in asthma. Am J Physiol Lung Cell Mol Physiol 302: L300-307.
46. Miller ES, Klinger JC, Akin C, Koebel DA, Sonnenfeld G (1994) Inhibition of murine splenic T lymphocyte proliferation by 2-deoxy-D-glucose-induced metabolic stress. J Neuroimmunol 52: 165-173.
47. Dreau D, Morton DS, Foster M, Fowler N, Sonnenfeld G (1998) Effects of 2-deoxy-D-glucose administration on immune parameters in mice. Immunopharmacology 39: 201-213. (Pubitemid 28432064)
48. Wu M, Neilson A, Swift AL, Moran R, Tamagnine J, et al. (2007) Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells. Am J Physiol Cell Physiol 292: C125-136. (Pubitemid 46115126)