T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks

eLife

Volumn 2014, Issue 3, 2014, Pages

  Tkach, Karen E ^a,b   Barik, Debashis ^a,d   Voisinne, Guillaume ^a   Malandro, Nicole ^a,b   Hathorn, Matthew M ^a,b   Cotari, Jesse W ^a,b   Vogel, Robert ^a,b   Merghoub, Taha ^a   Wolchok, Jedd ^a   Krichevsky, Oleg ^c   Altan Bonnet, Grégoire ^a,b  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

^d UNIVERSITY OF HYDERABAD   (India)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 2 RECEPTOR BETA; INTERLEUKIN 2 RECEPTOR GAMMA; JANUS KINASE; MAJOR HISTOCOMPATIBILITY ANTIGEN; STAT5 PROTEIN; T LYMPHOCYTE RECEPTOR; LYMPHOCYTE ANTIGEN RECEPTOR; TUMOR ANTIGEN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGENICITY; ARTICLE; CELL POPULATION; COMPLEX FORMATION; COMPUTER MODEL; CONTROLLED STUDY; CYTOKINE PRODUCTION; ENZYME LINKED IMMUNOSORBENT ASSAY; FEEDBACK SYSTEM; FLOW CYTOMETRY; FLUORESCENCE ACTIVATED CELL SORTING; GENE EXPRESSION; MATHEMATICAL MODEL; MOUSE; NONHUMAN; PROTEIN INTERACTION; SIGNAL TRANSDUCTION; SPLEEN CELL; T LYMPHOCYTE ACTIVATION; TUMOR IMMUNITY; ANIMAL; BIOLOGICAL MODEL; C57BL MOUSE; CELL COMMUNICATION; CELL CULTURE; COCULTURE; COMPUTER SIMULATION; EXPERIMENTAL MELANOMA; GENETICS; GENOTYPE; IMMUNOLOGY; KINETICS; LYMPHOCYTE ACTIVATION; METABOLISM; NONLINEAR SYSTEM; PHENOTYPE; PHOSPHORYLATION; T LYMPHOCYTE SUBPOPULATION; TRANSGENIC MOUSE; TUMOR ASSOCIATED LEUKOCYTE;

ANIMALS; ANTIGENS; ANTIGENS, NEOPLASM; CELL COMMUNICATION; CELLS, CULTURED; COCULTURE TECHNIQUES; COMPUTER SIMULATION; FEEDBACK, PHYSIOLOGICAL; GENOTYPE; INTERLEUKIN-2; KINETICS; LYMPHOCYTE ACTIVATION; LYMPHOCYTES, TUMOR-INFILTRATING; MELANOMA, EXPERIMENTAL; MICE, INBRED C57BL; MICE, TRANSGENIC; MODELS, IMMUNOLOGICAL; NONLINEAR DYNAMICS; PHENOTYPE; PHOSPHORYLATION; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; STAT5 TRANSCRIPTION FACTOR; T-LYMPHOCYTE SUBSETS;

EID: 84898402411     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.01944     Document Type: Article

References (76)

1. Alon U. 2007. Network motifs: theory and experimental approaches. Nature Reviews Genetics 8:450-461. doi: 10.1038/nrg2102.
2. Altan-Bonnet G, Germain RN. 2005. Modeling T cell antigen discrimination based on feedback control of digital ERK responses. PLOS Biology 3:e356. doi: 10.1371/journal.pbio.0030356.
3. Althaus CL, De Boer RJ. 2008. Dynamics of immune escape during HIV/SIV infection. PLoS Computational Biology 4:e1000103. doi: 10.1371/journal.pcbi.1000103.
4. Artomov M, Kardar M, Chakraborty AK. 2010. Only signaling modules that discriminate sharply between stimulatory and nonstimulatory inputs require basal signaling for fast cellular responses. The Journal of Chemical Physics 133:105101. doi: 10.1063/1.3482813.
5. Bachmann MF, Wolint P, Walton S, Schwarz K, Oxenius A. 2007. Differential role of IL-2R signaling for CD8+ T cell responses in acute and chronic viral infections. European Journal of Immunology 37:1502-1512. doi: 10.1002/ eji.200637023.
6. Badovinac VP, Harty JT. 2002. CD8(+) T-cell homeostasis after infection: setting the 'curve'. Microbes and Infection 4:441-447.
7. Becker V, Schilling M, Bachmann J, Baumann U, Raue A, Maiwald T, Timmer J, Klingmuller U. 2010. Covering a broad dynamic range: information processing at the erythropoietin receptor. Science 328:1404-1408. doi: 10.1126/ science.1184913.
8. Boyman O, Sprent J. 2012. The role of interleukin-2 during homeostasis and activation of the immune system. Nature Reviews Immunology 12:180-190. doi: 10.1038/nri3156.
9. Bruniquel D, Schwartz RH. 2003. Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nature Immunology 4:235-240. doi: 10.1038/ni887.
10. Busse D, de la Rosa M, Hobiger K, Thurley K, Flossdorf M, Scheffold A, Höfer T. 2010. Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments. Proceedings of the National Academy of Sciences of the United States of America 107:3058-3063. doi: 10.1073/ pnas.0812851107.
11. Chakraborty AK, Das J, Zikherman J, Yang M, Govern CC, Ho M, Weiss A, Roose J. 2009. Molecular origin and functional consequences of digital signaling and hysteresis during Ras activation in lymphocytes. Science Signal 2:pt2. doi: 10.1126/scisignal.266pt2.
12. Cheong R, Rhee A, Wang CJ, Nemenman I, Levchenko A. 2011. Information transduction capacity of noisy biochemical signaling networks. Science 334:354-358. doi: 10.1126/science.1204553.
13. Ciupe SM, Ribeiro RM, Nelson PW, Perelson AS. 2007. Modeling the mechanisms of acute hepatitis B virus infection. Journal of Theoritical Biology 247:23-35. doi: 10.1016/j.jtbi.2007.02.017.
14. Corse E, Gottschalk RA, Krogsgaard M, Allison JP. 2010. Attenuated T cell responses to a high-potency ligand in vivo. PLOS Biology 8:e1000481. doi: 10.1371/journal.pbio.1000481.
15. Cotari JW, Voisinne G, Dar OE, Karabacak V, Altan-Bonnet G. 2013. Cell-to-cell variability analysis dissects the plasticity of signaling of common gamma chain cytokines in T cells. Science Signaling 6:ra17.
16. Dai L, Vorselen D, Korolev KS, Gore J. 2012. Generic indicators for loss of resilience before a tipping point leading to population collapse. Science 336:1175-1177. doi: 10.1126/science.1219805.
17. Das J, Ho M, Zikherman J, Govern C, Yang M, Weiss A, Chakraborty AK, Roose JP. 2009. Digital signaling and hysteresis characterize ras activation in lymphoid cells. Cell 136:337-351. doi: 10.1016/j. cell.2008.11.051.
18. Deenick EK, Gett AV, Hodgkin PD. 2003. Stochastic model of T cell proliferation: a calculus revealing IL-2 regulation of precursor frequencies, cell cycle time, and survival. Journal of Immunology 170:4963-4972.
19. Duprez V, Cornet V, Dautry-Varsat A. 1988. Down-regulation of high affinity interleukin 2 receptors in a human tumor T cell line. Interleukin 2 increases the rate of surface receptor decay. The Journal of Biological Chemistry 263:12860-12865.
20. Engelhardt JJ, Boldajipour B, Beemiller P, Pandurangi P, Sorensen C, Werb Z, Egeblad M, Krummel MF. 2012. Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. Cancer Cell 21:402-417. doi: 10.1016/j.ccr.2012.01.008.
21. Feinerman O, Jentsch G, Tkach KE, Coward JW, Hathorn MM, Sneddon MW, Emonet T, Smith KA, Altan-Bonnet G. 2010. Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response. Molecular Systems Biology 6:437. doi: 10.1038/msb.2010.90.
22. Feinerman O, Veiga J, Dorfman JR, Germain RN, Altan-Bonnet G. 2008. Variability and robustness in T cell activation from regulated heterogeneity in protein levels. Science 321:1081-1084. doi: 10.1126/ science.1158013.
23. Francois P, Voisinne G, Siggia ED, Altan-Bonnet G, Vergassola M. 2013. Phenotypic model for early T-cell activation displaying sensitivity, specificity, and antagonism. Proceedings of the National Academy of Sciences of the United States of America 110:E888-E897.
24. Garcia Z, Pradelli E, Celli S, Beuneu H, Simon A, Bousso P. 2007. Competition for antigen determines the stability of T cell-dendritic cell interactions during clonal expansion. Proceedings of the National Academy of Sciences of the United States of America 104:4553-4558. doi: 10.1073/pnas.0610019104.
25. Georgiou G, Ippolito GC, Beausang J, Busse CE, Wardemann H, Quake SR. 2014. The promise and challenge of high-throughput sequencing of the antibody repertoire. Nature Biotechnology 32:158-168. doi: 10.1038/ nbt.2782.
26. Hemar A, Subtil A, Lieb M, Morelon E, Hellio R, Dautry-Varsat A. 1995. Endocytosis of interleukin 2 receptors in human T lymphocytes: distinct intracellular localization and fate of the receptor alpha, beta, and gamma chains. The Journal of Cell Biology 129:55-64. doi: 10.1083/jcb.129.1.55.
27. Henrickson SE, Perro M, Loughhead SM, Senman B, Stutte S, Quigley M, Alexe G, Iannacone M, Flynn MP, Omid S, Jesneck JL, Imam S, Mempel TR, Mazo IB, Haining WN, von Andrian UH. 2013. Antigen availability determines CD8(+) T cell-dendritic cell interaction kinetics and memory fate decisions. Immunity 39:496-507. doi: 10.1016/j.immuni.2013.08.034.
28. Hindmarsh AC, Brown PN, Grant KE, Lee SL, Serban R, Shumaker DE, Woodward CS. 2005. SUNDIALS: Suite of nonlinear and differential/algebraic equation solvers. ACM Transactions on Mathematical Software 31:363-396.
29. Huang J, Brameshuber M, Zeng X, Xie J, Li QJ, Chien YH, Valitutti S, Davis MM. 2013. A single peptide- Major Histocompatibility complex ligand triggers digital cytokine secretion in CD4 T Cells. Immunity 39:846-857.
30. Huppa JB, Gleimer M, Sumen C, Davis MM. 2003. Continuous T cell receptor signaling required for synapse maintenance and full effector potential. Nature Immunology 4:749-755. doi: 10.1038/ni951.
31. Janes KA, Reinhardt HC, Yaffe MB. 2008. Cytokine-induced signaling networks prioritize dynamic range over signal strength. Cell 135:343-354. doi: 10.1016/j.cell.2008.08.034.
32. Jenkins MK, Moon JJ. 2012. The role of naive T cell precursor frequency and recruitment in dictating immune response magnitude. Journal of Immunology 188:4135-4140. doi: 10.4049/jimmunol.1102661.
33. Joncker NT, Helft J, Jacquet A, Premel V, Lantz O. 2006. Intratumor CD4 T-cell accumulation requires stronger priming than for expansion and lymphokine secretion. Cancer Research 66:5443-5451. doi: 10.1158/0008- 5472.CAN-05-3526.
34. Kalia V, Sarkar S, Subramaniam S, Haining WN, Smith KA, Ahmed R. 2010. Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. Immunity 32:91-103. doi: 10.1016/j.immuni.2009.11.010.
35. Kedl RM, Schaefer BC, Kappler JW, Marrack P. 2002. T cells down-modulate peptide-MHC complexes on APCs in vivo. Nature Immunology 3:27-32. doi: 10.1038/ni742.
36. Kemp ML, Wille L, Lewis CL, Nicholson LB, Lauffenburger DA. 2007. Quantitative network signal combinations downstream of TCR activation can predict IL-2 production response. Journal of Immunology 178:4984-4992.
37. Kosmrlj A, Read EL, Qi Y, Allen TM, Altfeld M, Deeks SG, Pereyra F, Carrington M, Walker BD, Chakraborty AK. 2010. Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection. Nature 465:350-354. doi: 10.1038/nature08997.
38. Lanzavecchia A, Sallusto F. 2001. Antigen decoding by T lymphocytes: from synapses to fate determination. Nature Immunology 2:487-492. doi: 10.1038/88678.
39. Lee IH, Li WP, Hisert KB, Ivashkiv LB. 1999. Inhibition of interleukin 2 signaling and signal transducer and activator of transcription (STAT)5 activation during T cell receptor-mediated feedback inhibition of T cell expansion. The Journal of Experimental Medicine 190:1263-1274. doi: 10.1084/jem.190.9.1263.
40. Liao W, Lin JX, Wang L, Li P, Leonard WJ. 2011. Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages. Nature Immunology 12:551-559. doi: 10.1038/ni.2030.
41. Long M, Adler AJ. 2006. Cutting edge: paracrine, but not autocrine, IL-2 signaling is sustained during early antiviral CD4 T cell response. Journal of Immunology 177:4257-4261.
42. Mangan S, Alon U. 2003. Structure and function of the feed-forward loop network motif. Proceedings of the National Academy of Sciences of the United States of America 100:11980-11985. doi: 10.1073/ pnas.2133841100.
43. McNally A, Hill GR, Sparwasser T, Thomas R, Steptoe RJ. 2011. CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis. Proceedings of the National Academy of Sciences of the United States of America 108:7529-7534. doi: 10.1073/pnas.1103782108.
44. Mora T, Walczak AM, Bialek W., Callan CG Jnr. 2010. Maximum entropy models for antibody diversity. Proceedings of the National Academy of Sciences of the United States of America 107:5405-5410. doi: 10.1073/ pnas.1001705107.
45. Muranski P, Boni A, Antony PA, Cassard L, Irvine KR, Kaiser A, Paulos CM, Palmer DC, Touloukian CE, Ptak K, Gattinoni L, Wrzesinski C, Hinrichs CS, Kerstann KW, Feigenbaum L, Chan CC, Restifo NP. 2008. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 112:362-373. doi: 10.1182/ blood-2007-11-120998.
46. Nandi B, Chatterjee M, Hogle K, McLaughlin M, MacNamara K, Racine R, Winslow GM. 2009. Antigen display, T-cell activation, and immune evasion during acute and chronic ehrlichiosis. Infection and Immunity 77:4643-4653. doi: 10.1128/IAI.01433-08.
47. Nealson KH. 1977. Autoinduction of bacterial luciferase. Occurrence, mechanism and significance. Archives of Microbiology 112:73-79.
48. Nevozhay D, Adams RM, Murphy KF, Josic K, Balazsi G. 2009. Negative autoregulation linearizes the dose-response and suppresses the heterogeneity of gene expression. Proceedings of the National Academy of Sciences of the United States of America 106:5123-5128. doi: 10.1073/pnas.0809901106.
49. Obar JJ, Molloy MJ, Jellison ER, Stoklasek TA, Zhang W, Usherwood EJ, Lefrancois L. 2010. CD4+ T cell regulation of CD25 expression controls development of short-lived effector CD8+ T cells in primary and secondary responses. Proceedings of the National Academy of Sciences of the United States of America 107:193-198. doi: 10.1073/pnas.0909945107.
50. O'Garra A, Gabrysova L, Spits H. 2011. Quantitative events determine the differentiation and function of helper T cells. Nature Immunology 12:288-294. doi: 10.1038/ni.2003.
51. Pipkin ME, Sacks JA, Cruz-Guilloty F, Lichtenheld MG, Bevan MJ, Rao A. 2010. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity 32:79-90. doi: 10.1016/j.immuni.2009.11.012.
52. Podtschaske M, Benary U, Zwinger S, Hofer T, Radbruch A, Baumgrass R. 2007. Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression. PLOS ONE 2:e935. doi: 10.1371/ journal.pone.0000935.
53. Quiel J, Caucheteux S, Laurence A, Singh NJ, Bocharov G, Ben-Sasson SZ, Grossman Z, Paul WE. 2011. Antigen-stimulated CD4 T-cell expansion is inversely and log-linearly related to precursor number. Proceedings of the National Academy of Sciences of the United States of America 108:3312-3317. doi: 10.1073/ pnas.1018525108.
54. Rickert M, Boulanger MJ, Goriatcheva N, Garcia KC. 2004. Compensatory energetic mechanisms mediating the assembly of signaling complexes between interleukin-2 and its alpha, beta, and gamma(c) receptors. Journal of Molecular Biology 339:1115-1128. doi: 10.1016/j.jmb.2004.04.038.
55. Schulz EG, Mariani L, Radbruch A, Hofer T. 2009. Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Immunity 30:673-683. doi: 10.1016/j.immuni.2009.03.013.
56. Sheldon A, Flego L, Zola H. 1993. Coexpression of IL-2 receptor p55 and p75 by circulating blood lymphocytes. Journal of Leukocyte Biology 54:161.
57. Smith KA, Cantrell DA. 1985. Interleukin 2 regulates its own receptors. Proceedings of the National Academy of Sciences of the United States of America 82:864-868.
58. Smith KA. 1988. Interleukin-2: inception, impact, and implications. Science 240:1169-1176.
59. Smith AL, Wikstrom ME, Fazekas de St Groth B. 2000. Visualizing T cell competition for peptide/MHC complexes: a specific mechanism to minimize the effect of precursor frequency. Immunity 13:783-794.
60. Sojka DK, Bruniquel D, Schwartz RH, Singh NJ. 2004. IL-2 secretion by CD4+ T cells in vivo is rapid, transient, and influenced by TCR-specific competition. Journal of Immunology 172:6136-6143.
61. Sontag E, Kiyatkin A, Kholodenko BN. 2004. Inferring dynamic architecture of cellular networks using time series of gene expression, protein and metabolite data. Bioinformatics 20:1877-1886. doi: 10.1093/bioinformatics/ bth173.
62. Tay S, Hughey JJ, Lee TK, Lipniacki T, Quake SR, Covert MW. 2010. Single-cell NF-kappaB dynamics reveal digital activation and analogue information processing. Nature 466:267-271. doi: 10.1038/nature09145.
63. Tkach KE, Altan-Bonnet G. 2012. T cell responses to antigen: hasty proposals resolved through long engagements. Current Opinion in Immunology 25:1-6. doi: 10.1016/j.coi.2012.12.001.
64. Tubo NJ, Pagan AJ, Taylor JJ, Nelson RW, Linehan JL, Ertelt JM, Huseby ES, Way SS, Jenkins MK. 2013. Single naive CD4+ T cells from a diverse repertoire produce different effector cell types during infection. Cell 153:785-796. doi: 10.1016/j.cell.2013.04.007.
65. van Heijst JW, Gerlach C, Swart E, Sie D, Nunes-Alves C, Kerkhoven RM, Arens R, Correia-Neves M, Schepers K, Schumacher TN. 2009. Recruitment of antigen-specific CD8+ T cells in response to infection is markedly efficient. Science 325:1265-1269. doi: 10.1126/science.1175455.
66. Vilar JM, Kueh HY, Barkai N, Leibler S. 2002. Mechanisms of noise-resistance in genetic oscillators. Proceedings of the National Academy of Sciences of the United States of America 99:5988-5992. doi: 10.1073/ pnas.092133899.
67. Villarino AV, Tato CM, Stumhofer JS, Yao Z, Cui YK, Hennighausen L, O'Shea JJ, Hunter CA. 2007. Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals. The Journal of Experimental Medicine 204:65-71. doi: 10.1084/jem.20061198.
68. von Essen M, Bonefeld CM, Siersma V, Rasmussen AB, Lauritsen JP, Nielsen BL, Geisler C. 2004. Constitutive and ligand-induced TCR degradation. Journal of Immunology 173:384-393.
69. Wang HM, Smith KA. 1987. The interleukin 2 receptor. Functional consequences of its bimolecular structure. The Journal of Experimental Medicine 166:1055-1069.
70. Waysbort N., Russ D, Chain BM, Friedman N. 2013. Coupled IL-2-Dependent extracellular feedbacks Govern two distinct Consecutive phases of CD4 T Cell activation. Journal of Immunology 191:5822-5830. doi: 10.4049/ jimmunol.1301575.
71. Weinstein JA, Jiang N, White RA III, Fisher DS, Quake SR. 2009. High-throughput sequencing of the zebrafish antibody repertoire. Science 324:807-810. doi: 10.1126/science.1170020.
72. Williams MA, Tyznik AJ, Bevan MJ. 2006. Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature 441:890-893. doi: 10.1038/nature04790.
73. Yamane H, Paul WE. 2012. Cytokines of the gamma(c) family control CD4(+) T cell differentiation and function. Nature Immunology 13:1037-1044. doi: 10.1038/ni.2431.
74. Yamane H, Zhu J, Paul WE. 2005. Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment. The Journal of Experimental Medicine 202:793-804. doi: 10.1084/ jem.20051304.
75. Yosef N, Shalek AK, Gaublomme JT, Jin H, Lee Y, Awasthi A, Wu C, Karwacz K, Xiao S, Jorgolli M, Gennert D, Satija R, Shakya A, Lu DY, Trombetta JJ, Pillai MR, Ratcliffe PJ, Coleman ML, Bix M, Tantin D, Park H, Kuchroo VK, Regev A. 2013. Dynamic regulatory network controlling TH17 cell differentiation. Nature 496:461-468. doi: 10.1038/nature11981.
76. Zehn D, Lee SY, Bevan MJ. 2009. Complete but curtailed T-cell response to very low-affinity antigen. Nature 458:211-214. doi: 10.1038/nature07657.